Courtesy of Dr. Neel Patel If the rash is epidermal or a combination, try to define the characteristics of the rash. Is it mainly papulosquamous? Papulopustular? Blistering? After defining the characteristics, then think about causes of that type of rash: CITES MVA PITA: Congenital, Infections, Tumor, Endocrinologic, Solar related, Metabolic, Vascular, Allergic, Psychiatric, Latrogenic, Trauma, Autoimmune. When generating the differential, take the history and location of the rash into account. Source: http://www.mayoclinic.org/dermatology‐rst/immunofaqs.html False negative in BP: (i) low yield of biopsy on distal extremity (esp. legs) (controversial) and (ii) predominantly IgG4 subclass of auto‐antibody (poorly recognized on DIF) False positive in LE: chronically sun‐exposed skin of young adults To increase DIF yield: transport in saline (reduces dermal background) – cannot do DIF on formalin‐fixed specimen Source: Adapted from Comprehensive Laboratory Disease Workups. Graham PM, Wilchowski S and Fivenson D. Directions in Residency. Spring 2016, pp.1–4. Classification of cicatricial alopecia Source: Adapted from Olsen EA, et al. North American Hair Research Society Summary of Sponsored Workshop on Cicatricial Alopecia. J Am Acad Dermatol. 2003;48:103–110. Structural hair abnormalities by hair fragility Source: Adapted from Hordinsky MK. Alopecias. In: Bolognia JL, Jorizzo JL, Rapini RP. Dermatology Vol. 1, Mosby; London. 2003, p. 1042. Trichotillomania: pigment casts, trichomalacia, catagen hairs, dermal hemorrhage Androgenetic alopecia: miniaturized follicles Consider checking “nutrition labs” – Vitamin D, thiamine, zinc, total protein *Vellus hairs – true vellus hairs (small and lack melanin) and miniaturized terminal hairs – histologically identical. Associated with nail pitting, exclamation point hair, and yellow dots on dermoscopy No approved FDA treatment. Guided by age of pt, location of loss, disease extent, disease activity, other medical issues, and pt choice Adapted from Letsinger et al. J Am Acad Dermatol. 2005 Mar;52(3 Pt 1):500–508. Local factors promoting aphthae: chemical/mechanical injury, sodium lauryl sulfate‐containing dental products, inadequate saliva, and cessation of tobacco Source: Adapted from Freiman et al. J Cutaneous Med Surg 2006; 10(4). (From Sheth VM and Pandya AG. JAAD 2011;65: 689–697) [Forehead] [L malar] [R malar] [chin] Score range 0–48 Adapted from the American College of Rheumatology 1982 revised criteria Mucocutaneous Systemic Clinical findings: transient butterfly malar rash, generalized photosensitive eruption, and/or bullous lesions on the face, neck, and upper trunk. Associated with HLA‐DR2, HLA‐DR3 DIF: granular IgG/IgM (rare IgA) + complement at DEJ Clinical findings: psoriasiform or annular non‐scarring plaques in a photodistribution. Associated with: DIF: granular pattern of IgG/IgM in the epidermis only (variable) Clinical findings: erythematous plaques which progress to atrophic patches with follicular plugging, scarring, and alopecia on sun‐exposed skin. Progression to SLE: 5% if above the neck; 20% if above and below the neck DIF: granular IgG/IgM (rare IgA) + complement at DEJ, more likely positive in actively inflamed lesion present × 6–8 weeks Clinical findings: deep painful erythematous plaques, nodules, and ulcers involving proximal extremities and trunk. Overlying skin may have DLE changes. Progression to SLE: 50% DIF: rare granular deposits at the DEJ. May have deposits around dermal vessels. Clinical findings: erythematous indurations of fat with no scale or follicular plugs. DIF: nonspecific Lupus band: strong continuous antibody deposits at the DEJ on nonlesional skin; found in >75% of SLE patients on sun‐exposed skin and 50% SLE patients on non‐sun‐exposed skin Sensitivity and specificity for different antibiodies varies depending on the assay used. The % reported here are estimated averages from the referenced text below. * Correlates with SLE activity and renal disease. ** Risk of neonatal lupus among babies of SS‐A+ mothers: 2–6%. ANA titers of 1:80, 1:160, and 1:320 are found in 13, 5, and 3%, respectively, of healthy individuals. Among healthy elderly patients, ANA titers of 1:160 may be seen in 15%. Sheldon J. Laboratory testing in autoimmune rheumatic disease. Best Pract Res Clin Rheumatol. 2004 Jun;18(3): 249–269. Lyons et al. Effective use of autoantibody tests in the diagnosis of systemic autoimmune disease. Ann N Y Acad Sci. 2005 Jun;1050:217–228. Kurien BT, Scofield RH. Autoantibody determination in the diagnosis of systemic lupus erythematosus. Scand J Immunol. 2006 Sep;64(3):227–235. Habash‐Bseiso et al. Serologic testing in connective tissue diseases. Clin Med Res. 2005 Aug;3(3):190–193. Source: Adapted from Jacobe H et al. Autoantibodies encountered in patients with autoimmune connective diseases. In: Bolognia J, et al. Dermatology. Philadephia: Elsevier; 2003. pp. 589–599. * Antiphospholipid antibody (APA) syndrome – Primary (50%), SLE (35%); Skin: livedo reticularis, ulcers, gangrene, and splinter hemorrhages. Diagnosis requires at least one clinical criterion: And at least one lab criterion: anticardiolipin, lupus anticoagulant, or anti‐β2‐glycoprotein I Abs on 2 occasions six weeks apart. ** Polymyositis/Dermatomyositis – ≥0% ANA+, 90% auto‐Ab. Anti‐synthetase syndrome (tRNA): ILD, fever, arthritis, Raynaud disease, and machinist hands. (Sn: sensitive Sp: specific) *Drug‐induced (“Dusting Pattern”): Allopurinol, aldomet, ACE‐I, chlopromazine, clonidine, danazol, dilantin, ethosuximide, griseofulvin, hydralazine, isoniazid, lithium, lovastatin, mephenytoin, mesalazine, methyldopa, MCN, OCP, para‐amino salicylic acid, penicillamine, PCN, phenothiazine, pheylbutazone, piroxicam, practolol, procainamide, propylthiouracil, quinidine, streptomycin, sulfasalazine, sulfonamides, tegretol, and TCN. C‐ANCA = cytoplasmic (IIF) = proteinase 3. P‐ANCA = perinuclear (IIF) = myeloperoxidase. Other conditions which may be ANCA positive: SLE, RA, chronic infection (TB, HIV), digestive disorders (infl ammatory bowel disease, sclerosing cholangitis, primary biliary cirrhosis, autoimmune hepatitis), drugs (propylthiouracil, hydralazine, methimazole, minocycline, carbimazole, penicillamine), silica/occupational solvents Titers might indicate disease activity, relapse. Frequent life‐severe adverse events with cyclophosphamide (Cytoxan), nitrogen mustard, and alkylating agent: Initial workup: Detailed history, physical exam, ROS, skin biopsy ± DIF, CBC, ESR, BMP, UA, consider drug‐induced vasculitis. Further studies guided by ROS and type of vasculitis suspected: CRP, SPEP, UPEP, cryo, LFT, HBV, HCV, RF, C3, C4, CH50, ANA, ANCA, ASO, CXR, guaiac, cancer screening, HIV, ENA, echo, electromyogram, nerve conduction, biopsy (nerve, respiratory tract, kidney) Other causes of vasculitis: Infections (bacterial – meningococcemia, gonnococcemia, strep, mycobacterial; viral – HSV; fungal), Rheumatoid vasculitis, drug‐induced, Lupus, Paraneoplastic, Buerger, and Mondor. Lymphocytic vasculitis: Pityriasis lichenoides, Pigmented purpuras, Gyrate erythemas, Collagen vascular dz, Degos, Perniosis, Rickettsial, TRAPS Neutrophilic dermatoses: Sweet, Marshall (+ acquired cutis laxa), Behcet, Rheumatoid, Bowel‐associated dermatosis–arthritis syndrome. Vasculo‐occlusive/Microangiopathies: Cryos, Anti‐phospholip syndrome, Atrophic blanche/Livedoid, DIC, Purpura fulminans, Coumadin necrosis, TTP, Sneddon (livedo reticularis + cerebrovascular ischemia), Cholesterol emboli, CADASIL, Calciphylaxis, and Amyloid. Rheumatoid factor = Antibody against Fc portion of IgG = Cryoglobulinemia Types 2 (monoclonal RF) and 3 (polyclonal RF) Meltzer Triad = Purpura, arthralgia, and weakness Workup: Serum specimen must be obtained in WARM tubes. Immunoglobulins precipitate at cold temperature. Type 1 precipitates in 24 hours, Type 3 may require 7 days. Cryoglobulinemia: Immunoglobulins which reversibly precipitate on cold exposure Cryofibrinogen: Fibrinogen, fibrin, and fibronectin which precipitate in the cold Cold agglutinins: IgM antibodies which promote agglutination of RBCs on exposure to cold, triggering complement activation and lysis of RBCs. All three groups cause occlusive syndromes in the skin triggered by cold exposure. Acantholysis – P. vulgaris, P. vegetans, Hailey–Hailey, and acantholytic AK Acantholysis + dyskeratosis – Darier, Grover, paraneoplastic pemphigus, and warty dyskeratoma Other blistering diseases with acantholysis – SSSS, P. foliaceous Two types of P. vegetans: Should distinguish P. vegetans from pyodermatitis–pyostomatitis vegetans – associated with IBD, DIF‐ From JL Bolognia, JL Jorizzo, RP Rapini [Editors], Dermatology. Elselvier, 1st Edition, 2003. p. 436, Figure 30.2, with permission. Simplex (“epidermolytic EB”) – split basal layer tonofilament clumping in basal layer on EM, 40% of EB patients, sxs worse in summer/heat, typically no scarring and not severe (except Dowling–Meara and AR forms) Localized forms: Generalized forms: Junctional – split lamina lucida, defect in hemidesmosome, <10% of EB patients, oral lesions, absent/dystrophic nails, dysplastic teeth, usually no scarring/milia Dystrophic (“dermolytic EB”) – split sublamina densa (papillary dermis), >50% of EB patients, defective anchoring fibers, scars and milia. Dominant dystrophic EB: manifest at birth, bullae on extensor surfaces, (+) Nikolsky, (onion) scars and atrophy, milia on ears, hands, arms, and legs, mucous membrane/esophagus involved, nail dystrophy, scarring tip of tongue, improve w/ time. Recessive dystrophic EB *Tumorigenesis in RDEB is increased with production/retention of Col VII containing the NC1 domain (in laminin five‐dependent process). Non‐EB genodermatoses with infantile bullae: Kindler, Ichthyosis Bullosa of Siemens, BCIE, Gunther Classical pathway: C1qrs, C1 INH, C4, C2, C3 Activated by: antibody–antigen complex IgM > IgG (except IgG4 does not bind C1q) Alternative pathway: C3, Properdin, factor B, D Activated by: pathogen surfaces Lectin pathway: Mannan‐binding lectin and ficolins serve as opsonins, analogous to C1qrs. Leads to activation of the classical pathway without antibody. Activated by: pathogen surfaces Membrane attack complex: C5–9 C3NeF: Autoantibody that stabilizes bound C3 convertase (C3Bb). IgG isotype against Factor H, inhibits its activity to also drive complement activation. Associated with mesangiocapillary GN and/or partial lipodystrophy. *HAE‐3 = estrogren‐dependent form **AAE‐1 = associated w/ B‐cell lymphoproliferation ***AAE‐2 = autoimmune form, Ab against C1‐INH Treatments: Most are AR, except hereditary angioneurotic edema (HAE) which is AD Biopsy for GVHD vs. lymphocyte recovery vs. drug eruption Marra, DE, et al. Tissue eosinophils and the perils of using skin biopsy specimens to distinguish between drug hypersensitivity and cutaneous graft‐versus ‐host disease. JAAD 2004, 51(4): 543–545. Zhou, Y et al. Clinica significance of skin biopsies in the diagnosis and management of graft vs host disease in early postallogeneic bone marrow transplantation. Arch Derm 2000, 136(6): 717–721. Adapted from Bolognia JL, Jorizzo JL, Schaffer JV. Dermatology. 3rd Edition. Elsevier; 2012. * Th17 and Treg differentiation are both TGFβ‐dependent, but retinoic acid inhibits Th17 and promotes Treg differentiation. * Specificity of apocrine vs. eccrine stains is controversial. Source: Adapted from Benjamin A. Solky, MD and Jennifer L. Jones, MD. Boards’ Fodder – Bones, Eyes, and Nails. Other infectious causes of genital ulcers: EBV, Amebiasis, Candida, TB, and Leishmaniasis. Non‐Infectious causes of genital ulcers: Behcet/Apthous, Crohn, Lichen Planus, Tumor, Lichen Sclerosis, Contact, Trauma, Factitial, Fixed drug (NSAIDs, metronidazole, sulfonamide, acetaminophen, TCN, phenytoin, OCPs, phenolphthalein, and barbiturates), Other meds (all‐trans‐retinoic acid, foscarnet), MAGIC syndrome, Cicatricial/Bullous pemphigoid, Hemangioma, EM/SJS/TEN. Direct microscopy: Cultures White piedra: Trichosporon. Soft mobile nodules, face, axilla, pubic, and tropical. Black piedra: Piedraia hortae. Hard nonmobile nodules, face, scalp, pubic, and temperate. Tinea nigra: Phaeoannellomyces (Hortaea) werneckii. Brown macules on the palms. Tinea versicolor: Malassezia furfur/Pityrosporum ovale. Hypo/hyperpigmented macules on trunk and extremities. DDx superficial bacterial infection Zoophilic and geographic dermatophytes elicit significant inflammation M. gypseum may or may not fluoresce; T. rubrum may be ecto‐ or endothrix E. floccosum and T. concentricum do NOT invade scalp hair SAF – systemic antifungal: amphoB, liposomal amphoB, fluconazole, itraconazole, voriconazole, and caspofungin. * Therefore HBV is susceptible to anti‐HIV medications. * Umblicated lesions DDx: molluscum, pox viruses, HSV, histoplasmosis, cryptococcosis, penicilliosis, perforating disorders, leprosy, and GA. Adapted from Benjamin A. Solky, MD and Jennifer L. Jones, MD. Boards’ Fodder – Viruses. Source: Adapted from Benjamin A. Solky, MD and Jennifer L. Jones, MD. Boards’ Fodder – Bugs and their Vectors. Treatment adapted from The Medical Letter 2004; 46(1189). Reactions X‐RXN: Formaldehyde‐releasing preservatives Source: Adapted from Goldenberg A, et al. Boards’ Fodder – Contact Dermatitis Allergens Summer 2015 and Washaw EM et al. Dermatitis. 2015 Jan–Feb;26(1):49–59. * NACDG Rank Based on Table 8 Significance‐Prevalence Index Number from Warshaw et al. Dermatitis, 2015; 26:56–57. Urticaceae family (nettle): Euphorbiaceae family (spurge): Hydrophyllaceae family (water‐leaf) Hedera helix – Araliaceae – common ivy Opuntia spp. – Cactaceae – prickly pear Tulipa spp. – Liliaceae – tulip Ficus and Morus spp. – Moraceae – fig, mulberry Carduus and Cirsium spp. – Asteraceae – thistle Bidens tripartita – Asteraceae – bur marigold Other Asteraceae – dandelion, lettuce, chicory (irritant latex) Apiaceae: hogweed (Heracleum sphondylium), celery (Apium gaveolens), parsley (Petroselinum), parsnips, fennel (Foeniculum vulgare) Rutaceae: lime, orange, lemon, garden rue, Hawaiian lei, gas plant/burning bush Moraceae: mulberry, fig tree Fabaceae/Leguminosae: bavachee/scurf‐pea (vitiligo tx) Source: Modified from Willemze R, et al. WHO‐EORTC classification for cutaneous lymphoma. Blood. 2005;105: 3798. Based on 1905 patients with primary cutaneous lymphoma registered at the Dutch and Austrian Cutaneous Lymphoma Group 1986–2002. Alibert‐Bazin – classic type of MF Follicular MF – 10% of MF, folliculotropic infiltrates, follicular mucinosis, favors head and neck (esp eyebrow), alopecia, mucinorrhea, pruritic, stage as if classical tumor stage. Less responsive to skin‐directed therapies due to the deep follicular localization of MF infiltrate. Woringer‐Kolopp/Pagetoid Reticulosis – <1% of CTCL, localized, solitary hyperkeratotic patch/plaque, slowly progressive. Good prognosis – No reports of extracutaneous dissemination or disease‐related deaths. Ketron‐Goodmann – disseminated pagetoid reticulosis, aggressive. Granulomatous Slack Skin – pendulous atrophic lax skin, esp. axillae and groin. Associated with MF or Hodgkin lymphoma in 1/3 of cases. Usually indolent, very rare. Sezary – 5% of MF cases, triad of exfoliative erythoderma, lymphadenopathy, and atypical circulating (“Sezary,” “Lutzner,” or “mycosis”) cells. MF‐like immunophenotype but characteristically CD26‐ and CD3+ but diminished. Change from Th1 to Th2 profile may drive progression to Sezary. *Adapted from Kim YH. Mycosis fungoides and the Sezary syndrome. Semin Oncol 1999;26:276–289. Kim YH et al. Long‐term outcome of 525 patients with mycosis fungoides and Sezary syndrome. Arch Dermatol. 2003;139:857–866. Amin, Mahul, et al. AJCC Cancer Staging Manual, 8th Ed. Springer International Publishing, 2017. NCCN Guidelines Version 4.2018. Source: Modified from: Whittaker SJ, et al. Joint British Association of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines for the management of primary cutaneous T‐cell lymphomas. Br J Dermatol 2003 Dec;149(6):1095–1107 and Trautinger F, et al. EORTC Consensus Recommendations for the Treatment of Mycosis Fungoides/Sézary Syndrome. Eur J Cancer 2006 May; 42(8):1014–1030 SDT: Skin‐directed therapy: Emollients, Topical steroids, Nitrogen mutard (Mechlorethamine/HN2, Carmustine/BCNU), Bexarotene gel, Imiquimod, Topical MTX. ECP: Extracorporeal photopheresis TSEB: Total skin electron beam PBSCT: Peripheral blood stem cell transplant Denileukin diftitox = IL‐2/Diptheria toxin fusion. Acitretin = Retinoic acid receptor. 25–50 mg/d Baxarotene = Retinoid X receptor specific. 300 mg/m2/d Vorinostat = Suberoylanilide hydroxamic acid, SAHA. Histone deacetylase inhibitor. 400 mg po qd with food. May decrease to 300 QD if intolerant. Alemtuzumab (Campath) = anti‐CD52 Zanolimumab = HuMax‐CD4 *Secondary cutaneous follicle center lymphoma – BCL2+ BCL6+ CD10+ with t(14;18) PREVALENCE: 20–25% of primary cutaneous lymphomas are B‐cell lymphomas, each of the three major types representing ≤10% of cutaneous lymphomas. Source: Daoud et al. Monoclonal gammopathies and associated skin disorders. J Am Acad Dermatol. 1999;40(4):507–535. *Melanomas from skin without chronic photodamage – BRAF and NRAS mutations but nl CDK4 and CCND1 vs. Melanomas from skin with chronic photodamage – increase in number of CDK4 and CCND1 but nl BRAF and NRAS vs. Melanomas from non‐sun‐exposed skin (acral, mucosal) – KIT mutations but nl BRAF and NRAS; Acral MMs have higher degrees of chromosomal aberrations; p53 mutations uncommon in MM except LMM or MM associated with XP‐C or Li‐Fraumeni. CDKN2A mutations also found late in sporadic tumors. BRAF‐positive mutated melanomas can be treated with vemurafenib, dabrafenib, and other agents that may increase survival. Stains: PAS +/diastase resistant. + Thioflavin T. Purple with crystal violet. Birefringence with Congo red (absent after treating with potassium permanganate in AA subtype). May have anemia, leukopenia, elevated ESR, and 20% HSM Familial HLH: Source: Susan B. Mallory. An Illustrated Dictionary of Dermatologic Syndromes, Second Edition, Taylor & Francis, 2006. * Other familial hypercholesterolemia syndromes – AR hypercholesterolemia (ARH/LDLR adaptor protein mutations), AD hypercholesterolemia type 3 (PCSK9/PROPROTEIN CONVERTASE, SUBTILISIN/KEXIN‐TYPE, 9 mutations). Vitamin A supplementation helpful in rubeola Deficiency = Phrynoderma (toadskin) Hypervitaminosis A Deficiency = Beriberi Deficiency Deficiency = Pellagra Deficiency Deficiency Deficiency = Scurvy Physiology: Deficiency Hypervitaminosis D Deficiency (From Cheng CE, Friedlander, SF. Semin Cut Med Surg 2015;35: 108–116) Diagnosis: made based on medical history and clinical features Need MRI head and neck (including aortic arch) and ECHO prior to starting propranolol (From Hoeger PH, Harper JI, Baselga E. et al. Eur J Pediatr 2015;174: 855.)
Part 1
General Dermatology
COMMON WORK‐UPS, SIGNS, AND MANAGEMENT
Dermatologic Differential Algorithm
Direct Immunofluorescence (Dif)
Diseases
Where to biopsy
LE, MCTD, PCT, LP, vasculitis
Erythematous border of active lesion/involved skin (avoid old lesions, facial lesions, and ulcers)
Pemphigus group, pemphigoid group, linear IgA
Erythematous perilesional skin (avoid bullae, ulcers, and erosions)
DH
Normal‐looking perilesional skin (0.5–1 cm away)
Lupus band
Uninvolved, non‐photoexposed skin (buttock)
False positive/negative DIFs:
Workup Quick Reference Orders (guided by clinical presentation)
Acanthosis
nigricans
CBC/CMP, lipid panel, HgA1C, TSH, CEA, LH/FSH
Alopecia
(see “Alopecia Workup, p. 6–9 for further details)
CBC/CMP, Fe/TIBC/Ferritin, TSH, free and total testosterone, 17‐OH progesterone, VDRL,FSH, LH, DHEA‐S, ANA, ESR, prolactin, Vitamin D
Anetoderma
CBC, ANA, anti‐dsDNA, anti‐SSA/B, TSH, RPR, Lyme titer, HIV, fasting AM cortisol, C3/C4/CH50, protein C/S, anti‐thrombin III, anti‐cardiolipin abs, lupus anticoagulant, B2‐glycoprotein
Angioedema
CBC, C1 est inhib, C1,C2,C4
Hereditary: C1‐nl; C2,C4,C1 est inhib‐ ↓ (C1‐INH levels may be nl but nonfunctional)
Acquired: C1‐↓; C2,C4,C1 est inhib‐ ↓
CTCL
CBC with peripheral smear (Sezary Prep), AST/ALT, LDH, CXR, HIV, HTLV‐1, CD4/8 flow cytometry (CD5, CD7, CD45RO, CD26: CTCL protocol)
Dermatitis herpetiformis
anti TTG‐IgG, IgA > endomysial ab, anti‐Gliadin ab (IgG and IgA), total IgA, CBC, CMP, Vitamin D
Dermatomyositis
Antisynthetase panel: (Anti‐Jo‐1 PL‐7, EJ, OJ
PL‐12), anti‐Mi‐2, CK, aldolase, LDH, CRP, anti‐SRP
PFTs, anti‐aminoacyl‐tRNA synthetases (interstitial lung disease (ILD) association), anti P‐155 (cancer association), anti‐CADM (ILD association), anti‐MDA5 (RA‐like associations)
Flushing
24‐hour urine 5‐HIAA and metanephrines, norepinephrine, VMA, prostaglandin D2, dopamine, tryptase, histamine, plasma VIP, UA, serotonin, calcitonin (if thyroid nodule)
Hypercoagulability and thrombogenic vasculopathy
ANA, protein C/S, lupus anticoagulant, anti‐phospholipid ab, β2 glycoprotein ab, anti‐cardiolipin, hepatitis B/C, SPEP/UPEP, Factor V Leiden, prothrombin gene mutation, homocysteine level, MTHFR gene mutation
Hyperhidrosis (diffuse/sudden)
CBC, HbA1c, cortisol, TSH, GH, serotonin, urine 5‐HIAA, urine 24‐hour catecholamines
LCV
ROS neg: CBC, CMP, UA, ANA, HBV/HCV, Skin Bx +/‐ DIF
ROS pos: add ANCA, Cryo, ASO, HBV, ESR, RF, Complement, age‐appropriate cancer screening
MCTD
Anti‐U1RNP, anti‐Ku, ANA, RF, CRP
PCOS
Total and free testosterone, DHEA‐S, LH/FSH, sex hormone‐binding globulin, β‐HCG
PCT/
pseudoporphyria
HCV, Fe, 24‐hour urine porphyrins (Uro:copro> 8:1), CBC, LFT, lead levels, quantitative plasma porphyrins, stool porphyrins
Photosensitivity
ANA, ENA (SSa/b)
Pruritus
CBC/CMP, LFTs, TSH, bilirubin, CXR, UA, hepatitis B/C, peripheral blood smear, Fe, β‐HCG, ESR, HIV
SPEP/UPEP, stool ova and parasite, age‐appropriate cancer screening
Purpura
CBC w/ peripheral smear, CMP, TSH, ANA, PT/PTT, bleeding time, c‐ANCA, p‐ANCA, SPEP/UPEP, cryoglobulins, vitamin K level, D‐dimer
Pyoderma gangrenosum
CBC/CMP, UA, peripheral smear, ANA, RF, SPEP/UPEP, ANCA, antiphospholipid ab, RF, colonoscopy, Hep B/C
Recurrent furunculosis/carbunculosis
Skin culture w/ gram stain, CMP, blood glucose, HIV, hepatitis B/C, CH50, peripheral smear, SPEP, IgG/IgM/IgE, nitroblue tetrazolium (if concern for CGD)
Sarcoidosis
CBC, CMP, Ca+, Serum ACE level, 1,25 Vit D, PTH, Alk Phos, ESR, ANA, CXR, QuantiFERON Gold
Scleroderma/CREST syndrome
Anti‐Scl‐70, ANA, anti‐Jo‐1, anti‐centromere, RNA, polymerase I/III, RF, esophageal motility, PFTs, BUN/creatinine
Sjogren’s syndrome
ANA, anti‐Ro/La, CRP, RF, anti‐alpha‐fodrin ab
Syphilis
RPR/VDRL – primary; FTA‐ABS – secondary
SLE
CBC/CMP, ANA, anti‐smith, dsDNA, UA, BUN/creatinine, ESR, ENA panel, C3/C4/CH50
TEN
Check for IgA deficiency if Tx = IVIG as GammaGard needed (IgA depleted):
IVIG 2–4 g/kg (total dose, divided over 2–5 d, see TEN protocol pg. 227
Urticaria
CBC, IgE, anti‐FcεRI (CUI), sinus X‐ray, hepatitis B/C, TSH, anti‐TPO, anti‐thyroglobulin, H. pylori, cryoglobulins
In children often due to strep: Check ASO, Rapid Strep
Urticarial vasculitis
ESR, C4/CH50, anti‐FcεRI (CUI), anti‐C1q, ASO, RF, ANA, UA, SPEP, Hep B/C, CRP, C3/C4/CH50
Vitiligo
CBC, TSH/Free T4, anti‐thyroid peroxidase (TPO), fasting blood glucose, 25‐OH Vitamin D, B12/folic acid, anti‐parietal gastric cell antibody (APGC)
Alopecia Workup
Hair
Duration
% of hair
Microscopic/hair pull
Anagen
2–6 yr
85–90
Sheaths attached to roots
Catagen
2–3 wk
<1
Intermediate appearance (transitional)
Telogen
3 mo
10–15
Tiny bulbs without sheaths, “club” root
Exogen
Active shedding of hair shaft
Kenogen
Rest period after shedding telogen; empty follicle
Breakage
Coming out at roots
Hair shaft defects, trichorrhexis nodosa, hair care (products, traction, and friction), tinea capitis, trichotillomania, anagen arrest/chemotherapy
Telogen effluvium, alopecia areata, androgenetic, syphilis, loose anagen, OCPs
Focal loss
Diffuse loss
Hair care (traction), tinea capitis, trichotillomania, alopecia areata, syphilis, hair shaft defects
Telogen effluvium, anagen effluvium, androgenetic alopecia, hair shaft defects
Lymphocytic
Neutrophilic
Mixed
Increased fragility
No increased fragility
Trichorrhexis invaginata (bamboo)
Monilethrix
Trichorrhexis nodosa
Trichothiodystrophy
Pili torti
Loose anagen
Pili annulati
Uncombable hair (spun‐glass)
Woolly hair
Pili bifurcati
Pili multigemini
Acquired progressive kinking
Disorder
Hair mount findings
Monilethrix
Beaded, pearl necklace, knots
Trichorrhexis nodosa
Fractures, paint brushes
Trichorrhexis invaginata
Bamboo/golf tee hair
Trichothiodystrophy
Trichoschisis, tiger‐tail on polarization
Loose anagen
Anagen hairs with ruffled cuticles and curled ends and lacking root sheaths
Pili torti
Flattened, 180° irregularly spaced twists
Uncombable hair
Pili canaliculi et trianguli, triangular in cross‐section
Pili annulati
Abnormal dark bands on polarization, air bubbles in cortex
Elejalde
Pigment inclusions
Griscelli
Pigment clumping
Menkes
Multiple – pili torti, trichorrhexis nodosa, trichoptilosis
Ethnic differences in hair
Hair shaft structure
Hair shaft cross‐section
Others
African‐American
Coiled, curved
Elliptical, flattened
Lowest water content, slower growth, fewer cuticular layers at minor axes (only 1–2 not 6–8), longer major axis, less dense, large follicles
Asian
Straight
Circular
Largest follicular diameter; fewer eyelashes with lower lift‐up/curl‐up angles and greater diameter
Caucasian
In between
In between, oval
More dermal elastic fibers anchoring hair
Telogen effluvium – workup and treatment
Androgenic alopecia – workup and treatment
Alopecia areata – workup and treatment
Patchy AA
Extensive AA
Topical or IL corticosteroid
Steroid in shampoo
Minoxidil
Anthralin
Topical immunotherapy
Topical, IL, Oral corticosteroids
Anthralin
Minoxidil
Immunotherapy
Phototherapy/Excimer laser
Immunosuppressive‐MTX, CSA
Biologics
Other alopecia treatments
Aphthosis Workup and Treatment
Morphologic classification
Classification by cause
Workup for complex apthae
Treatment
Dermatologic Signs
Sign
Disease association
Site
Albright’s dimpling
Albright’s hereditary osteodystrophy
Dimpling over knuckles, enhanced by fist clenching
Albright’s
Nevoid BCC syndrome/Gorlin’s
Short fourth metacarpal digits
Asboe–Hansen
+: in pemphigus and other blistering dx (BP, DH, EBA, CP, DEB, bullous drug, SJS/TEN)
−: usually for Hailey–Hailey and Staph scalded Skin
Existing blister, extension to adjacent unblistered skin with mechanical pressure on top of bulla
Auspitz
Plaque psoriasis, but also Darier’s disease and actinic keratosis
Red, glossy surface with pinpoint bleeding on removal of the scale by scraping or scratching
Battle’s
Basal skull fracture
Discoloration at mastoid process
Blue dot
Torsion of testicular epididymis and appendices
Blue or black nodule visible under the skin on the superior aspect of the testis or epididymis and area will be tender
Butterfly
Lupus erythematosus on face; atopic dermatitis on upper back
Erythema over the malar eminence and nasal bridge; butterfly‐shaped area of sparing observed over the upper central back, corresponding to the zone that is difficult to reach by hands
Buttonhole
Cutaneous neurofibraomas, but also syphilitic chancre and old pigmented nevi
Invaginate the tumor into the underlying dermal defect with digital pressure
Cluster of jewels
Early stage of chronic bullous disease of childhood
New lesions at margin of older ones, aka “string of pearls, “rosettes sign”
Corn‐flake
Kyrle’s and Flegel’s diseases
Polygonal irregular configuration of lesions that tend to occur over the lower extremities
Crowe’s
Type II neurofibromatosis
Axillary freckling, may occur in perineum, typically appears later than café au lait macules
Darier’s
Condns with increased mast cells in the dermis (urticaria pigmentosa, systemic mastocytosis, insect bite reactions, neurofibroma, juvenile xanthogranuloma, acute neonatal lymphoblastic leukemia)
Whealing, circumferential erythema, and localized pruritis elicited by scratching or rubbing of a lesion
Deck chair
Cutaneous Waldenstrom’s macroglobulinemia
Widespread erupton of erythematous papules that coalesce into rectangular plaques. Sparing of the natural skin folds, resembling the slats of a deck chair
Dimple
Dermatofibromas
Lateral compression with the thumb and index finger leads to depression of the lesion. This dimpling is secondary to the lesion being attached to the subcutaneous fat
Dirty neck
Chronic atopic dermatitis
Reticulate pigmentation of the neck with the anterolateral aspects of the neck typically affected secondary to melanin incontinence
Doughnut
Scleromyxedema
Central depression surrounded by an elevated rim of skin on the extended proximal interphalagneal joint
Dubois’
Dermatitis artefacta
Produced by corrosive liquids. Patterned burned areas correspond to the areas of dripping of the liquid when applied by the patient
Ear lobe
Contact dermatitis
Substance applied with the hand to the face and neck leads to sparing of the diagonal crease of the ear lobe on the ipsilateral side, whereas the contralateral side is affected. Secondary to hand‐sweeping movement made during application of the substance
Enamel paint
Kwashiorkor
Sharply demarcated hyperpigmented desquamating patches and plaques resembling enamel paint occur on the skin, predominantly in areas of pressure and irritation
Exclamation mark hair
Alopecia areata
Proximal tapering of hair where the dot represents the remains of the bulb
Flag
Nutritional deficiencies (kwashiorkor) intermittent high dosage of methotrexate or following chemotherapy and ulcerative colitits
Horizontal alternating bands of discoloration in the hair shafts corresponding to periods of normal and abnormal hair growth. Discoloration may be reddish, blonde, gray, or white depending on the original hair color
Forchheimer’s
Rubella
Enanthem of red macules or petechiae confined to the soft palate
Frank’s
Coronary disease and coronary artery disease or retinopathy in DM type II
Diagonal groove across the ear lobe in adults
Gorlin’s
Ehlers–Danlos syndrome
Ability to touch the tip of the nose with the extended tongue
Gottron’s
Dermatomyositis, but also systemic lupus
Symmetric confluent macular violaceous erythema occurring over the knuckles, hips, knees, and medial ankles
Grey Turner’s
Acute hemorrhagic pancreatitis and other causes of retroperitoneal hemorrhage
Induration and bruising seen on the skin over the costovertebral angle secondary to the spread of blood from anterior pararenal space
Groove
Lymphogranuloma venereum in heterosexual males
Inflammatory mass of femoral and inguinal nodes separated by a depression or groove made by Poupart’s (inguinal) ligament
Hair collar
Neural tube closure defects on the scalp (such as aplasia cutis, encephalocele, meningocele, or hetertropic brain tissue)
Ring of dark coarse hair surrounding a malformation. Defect is typically midline and the occipital or parietal scalp is typically affected
Hanging curtain
Pityriasis rosea
When the skin is stretched across the long axis of the herald patch, the scale is noted to be finer, lighter, and attached at one end, which tends to fold across the line of the stretch
Heliotrope
Dermatomyositis
Violaceous erythema involving the periorbital skin
Hertoghe’s
Atopic dermatitis, trichotillomania, ectodermal dysplasia, alopecia areata, alopecia mucinosa, leprosy, syphilis, ulerythema ophryogenes, systemic sclerosis and hypothyroidism
Lack of hair at the outer 1/3 of the eyebrows
Hoagland’s
Infectious mononucleosis
Early and transient bilateral upper lid edema
Holster
Dermatomyositis
Pruritic, macular, violaceous erythema affecting the lateral aspects of the hips and thighs
Hutchinson’s nail
Subungual melanoma
Periungual extension of brown‐black pigmentation onto the proximal and/or lateral nail folds
Hutchinson’s nose
Herpes zoster
Presence of vesicles occurring on the tip of the nose
Jellinek’s
Hyperthyroidism
Hyperpigmentation of the eyelid
Leser–Trelat
Internal malignancy (typically adenocarcinomas, lung cancer, melanoma, and mycosis fungoides)
Sudden eruption of multiple seborrheic keratoses, which are often pruitic
Muehrcke’s
Nephritic syndrome, GN, liver disease, and malnutrition
Paired, transverse, narrowed white bands that run parallel to the lunula of the nails and are seen in patients with hypoalbuminemia or those receiving chemotherapy agents
Neck
Scleroderma
Ridging and tightening of the neck forming a visible and palpable tight band that lies over the platysma in the hyperextended neck
Necklace of casal
Pellagra
Hyperpigmentation on the neck extending as a broad collar‐like band around the entire circumference of the neck
Nikolsky’s
Pemphigous foliaceus
Pulling the ruptured wall of the blister it is possible to take off the horny layer for a long distance on a seemingly healthy skin and rubbing off of the epidermis between the bullae by slight friction without breaking the surface of the skin and leaving moist surface of the granular layer
Nose
Airbone contact dermatitis, severe atopic dermatitis, and exfoliative dermatitis
Sparing of the nose in the eruption distribution
Oil drop
Psoriasis
Translucent, yellow‐red discoloration and circular areas of onycholysis in the nail bed that fail to reach the free border and look like oil drops underneath the nail
Panda
Laser therapy complication
Nevus of Ota in the periorbital location
Pastia
Preeruptive stage of scarlet fever
Pink or red transverse lines found in the antecubital fossae and axillary folds
Pathergy
Pyoderma gangrenosum or Behcet’s syndrome
Elicitation of new lesions or worsening of existing lesions by superficial trauma
Racoon
Basilar skull fracture
Periorbital ecchymosis from subconjunctival hemorrhage
Romana’s
Chagas’ disease
First clinical sign of sensitization response to the bite of the Trypansoma cruzi insect presenting as severe unilateral conjunctivitis and palpable, painless lid edema
Rope
Interstitial granulomatous dermatitis with arthritis
Inflammatory indurations appearing like cords that extend from the lateral trunk to the axillae
Round fingerpad
Scleroderma
Disappearance of the peaked contour on the fingerpads and progression to a hemisphere‐like finger contour
Russell’s
Bulimia nervosa
Lacerations, abrasions, and callosities that are found on the dorsum of the hand overlying the metacarpophalangeal and interphalangeal joints due to repeated contact of the incisor teeth with the skin during self‐induced vomiting
School chair
Contact dermatitis to nickel
Rash occurring over the posterior thighs, corresponding to contact with a school chair
Shawl
Dermatomyositis
Vonfluent, symmetric, macular violaceous erythema on the posterior shoulders and neck, giving a distinctive shawl‐like appearance
Slapped cheek
Children with fifth disease
Confluent, erythematous, edematous plaques on the cheeks
Sternberg’s thumb
Arachnodactyly and Marfan syndrome
Completely opposed thumb in the clenched hand projects beyond the ulnar border
Tent
Benign appendageal tumor pilomatricoma
Solitary, asymptomatic, firm nodule. When the overlying skin is stretched, the lesion appears to be multifaceted and angulated, giving a “tent” appearance. The tent sign is due to calcification occurring in the lesion
Thumbprint
Disseminated strongyloidosis
Periumbilical purpura resembling multiple thumbprints
Tin‐tack
Discoid lupus erythematosus
Hyperkeratotic scale extending into the follicular infundibulum creates keratotic spikes when viewed from the scale’s undersurface, resembling a carpat tack
Tripe palms
Internal malignancy (carcinoma of the stomach and lung)
Rugose thickening of the palmar surface of the hands, with accentuation of the normal dermatoglyphic ridges, thus resembling the ridging of the interior surface of a bovine foregut
Trousseau’s
Visceral malignancy (predominantly pancreatic cancer)
Development of successive crops of tender nodules in affected blood vessels secondary to intravascular low‐grade hypercoagulation usually affecting upper extremities or trunk
Ugly duckling
Melanoma
A nevus that does not resemble a patient’s other nevi
V
Dermatomyositis
Erythema secondary to photosensitivity seen in the V area of the upper chest
Walzel
Acute and chronic pancreatitis
Livedo reticularis
Winterbottom’s
Gambian form of African trypanosomiasis
Occasionally visible enlargement of lymph nodes in the posterior cervical group
Folliculitis
Type
Clinical presentation
Treatment
Staph
Multiple follicular‐based erythematous papules/pusules
Mupirocin cream to nares
Chlorhexidine wash
Dicloxacillin or cephalexin for MSSA
Trimethoprim/sulfamethoxazole, clindamycin, or doxycycline for MRSA
Gram‐negative
Multiple small pustules in the perinasal region, chin, and cheeks. Classic scenario: acne patient treated with long‐term antibiotics
Isotretinoin
Ampicillin, trimethoprim/sulfamethoxazole, and ciprofloxacin
Pseudomonas
Exposure to contaminated water in pools/hot tub
Usually resolve without treatment in 7–10 d
Ciprofloxacin for severe cases
Demodex
Rosacea‐like papules and pustules with periorificial accentuation on a background of erythema. Facial perifollicular scaling.
Permetherin 5% cream
Metronidazole
Ivermectin
Pityrosporum
Very pruritic small monomorphous papules and pustules on upper trunk. Commonly found in hot and humid environment or with immunocompromised patient or those on long‐term antibiotics
Ketoconazole cream/shampoo
Selenium sulfide shampoo
May need systemic antifungals
Eosinophilic folliculitis
Tacrolimus 0.1% ointment
Cyclosporin
Indomethacin 25–75 mg qd for 1–8 wk
Isotretinoin
Metronidazole
Phototherapy
EGFR induced
Four stages of eruption – dysesthesia, erythema, edema; erythematous papules and pustules; purulent crusting; telangiectasia. Lesions can be painful and pruritic.
Doxycycline 200 QD prescribed with EGFR inhibitor to prevent folliculitis
Melasma
Principles of melasma therapy
IMMUNOLOGY AND IMMUNOLOGIC DISEASE
Lupus Erythematosus
Systemic lupus erythematosus criteria (4 of 11)
Acute cutaneous lupus erythematosus
Subacute cutaneous lupus erythematosus
Chronic cutaneous lupus erythematosus
Discoid lupus
Lupus panniculitis
Tumid lupus
Autoantibody
Autoantibody sensitivities and specificities
Condition
Autoantibody
Sensitivity (%)
Specificity (%)
SLE
ANA
93–99
57
Histone
60–80
50
dsDNA*
50–70
97
U1‐RNP
30–50
99
Ribosomal‐P
15–35
99
Sm
10–40
>95
SS‐A
10–50
>85
SS‐B
10–15
SCLE
ANA
67
SS‐A
60–80
SS‐B
25–50
DLE
ANA
5–25
SS‐A
≪̸10
Drug‐induced LE
ANA
>95
Histone
>95
dsDNA
1–5
Sm
1
Neonatal lupus
SS‐A**
95
SS‐B
60–80
MCTD
ANA
100
U1‐RNP
>95
Scleroderma
ANA
85–95
55
Scl‐70
15–70
100
U3‐RNP
12
96
Centromere
<10
CREST
Centromere
>80
Scl‐70
15
Progessive systemic sclerosis
Scl‐70
50
Centromere
<5
Sjögren
ANA
50–75
50
SS‐A
50–90
>85
SS‐B
40
>90
RF
50
Polymyositis (PM)
ANA
85
60 (DM/PM)
Jo‐1
25–37
Dermatomyositis (DM)
ANA
40‐80
60 (DM/PM)
Rheumatoid arthritis
CCP
65–70
90–98
RF
50–90
>80
ANA
20–50
55
Histone
15–20
Secondary Raynaud
ANA
65
40
Autoantibodies in connective tissue diseases
Autoantibody or target
Activity
Clinical association
LAC, β2‐glycoprotein I, Prothrombin, Cardiolipin, Protein S, and Annexin AV
Phospholipids
Antiphospholipid antibody syndrome*
Rheumatoid factor
Fc portion of IgG
Low level nonspecific (SLE, SSc, MCTD, neoplasm, chronic disease)
High level – associated with erosive RA
Ku
DNA end‐binding repair protein complex
Overlap DM/PM, SSc, LE
U2‐RNP
Overlap DM/PM, SSc
Alpha‐fodrin
Actin‐binding protein
Specific for Sjögren
Jo‐1/PL‐1
Histidyl‐tRNA synthetase
DM/PM** (20–40% sensitive) – increased risk of ILD, but no increased rate of malignancy
Mi‐2
Nuclear helicase
DM with malignancy, better prognosis than anti‐synthetase
PDGF
SSc, cGVHD
SRP
Signal recognition protein
Anti‐SRP syndrome (rapidly progressive necrotizing myopathy); association with cardiac disease not confirmed
155 K‐EB antigen
Transcriptional intermediary factor‐1
DM (20% sensitive in adult‐onset classical form), may be associated with internal malignancy
Anti‐nuclear antibodies
Pattern
Antibody target
Disease
Notes
Homogenous
Histone
Drug‐induced LE* (>90% Sn), SLE (>60% Sn), Chronic Dz
dsDNA
SLE (60% Sp), Lupus nephritis
IC in glomeruli = nephritis, follows disease activity, test performed on Crithidia luciliae
Peripheral nuclear (Rim)
Nuclear lamins
SLE, Linear Morphea
Nuclear pore
PM
Centromere/true speckled
Centromere
CREST (50–90% Sn), SSc, Primary billiary cirrhosis (50% Sn), Idiopathic Raynaud, PSS
Speckled/particulate nuclear
(ENA)
U1RNP
Mixed connective tissue disease (near 100% Sn)
SLE (30% Sn), DM/PM, SSc, Sjögren, RA
Titer > 1:1600 in 95–100% MCTD
Smith (snRNP)
SLE (99% Sp but only 20% Sn)
Ro/SS‐A (E3 ubiquitin ligase, TROVE2)
SCLE (75–90% Sn), Sjögren, Neonatal LE, Congenital Heart Block, C2/C4 deficient LE
Photosensitivity workup
La/SS‐B (binds RNA newly transcribed by RNA Pol III)
Sjögren, SCLE
Nucleolar
SCL‐70 (Topoisomerase I)
SSc (diffuse)
Poor prognosis
Fibrillarin (U3‐RNP)
SSc (localized > diffuse)
PM‐SCL
PM/SSc overlap syndromes
Machinists hands, arthritis, Raynaud, and calcinosis cutis
RNA Pol I
SSc
Poor prognosis, renal crisis
ANCA (Anti‐neutrophil cytoplasmic antibodies)
Granulomatosis with polyangiitis (formerly Wegener’s)
Microscopic polyangiitis
Churg–Strauss syndrome
ANCA (% sensitivity)
C‐ANCA (85%) > P‐ANCA (10%)
P‐ANCA (45–70%) > C‐ANCA (45%)
P‐ANCA (60%) > C‐ANCA (10%)
Classic features
Upper respiratory (sinusitis, oral ulcers, rhinorrhea), glomerulonephritis (GN), saddle‐nose, strawberry gingiva, ocular
Necrotizing GN (segmental and crescentic), pulmonary hemorrhage (esp. lower), neuropathy
Asthma, allergies, nasal polyps, eosinophilia, PNA, gastroenteritis, CHF, mononeuritis multiplex
Skin
Palpable purpura, SQ nodules, pyoderma gangrenosum‐like lesions
Palpable purpura
Palpable purpura, SQ nodules
Pathology
Perivascular necrotizing granulomas, LCV
No granulomas, LCV with few/no immune depositis
Eosinophils, extravascular granulomas, LCV
Respiratory
Upper and lower respiratory, fi xed nodular densities
Lower respiratory, alveolar hemorrhage
Patchy, transient interstitial infi ltrates
Treatment
High‐dose corticosteroids; Cytotoxic agents if severe (no controlled trial demonstrating benefi ts)
High‐dose corticosteroids; Cytotoxic agents if severe (no controlled trial demonstrating benefi ts)
High‐dose corticosteroids combined with cytotoxic agent (cyclopohsphamide) with proven benefi t in survival
Treatment of ANCA‐associated vasculitis
Vasculitis
Small vessel vasculitis
Disease
Symptoms
Etiology Associations
Treatment
Cutaneous small vessel vasculitis
Palpable purpura, lower legs/ankles/dependent areas, +/– livedo reticularis, urticaria, edema, ulcers, +/– pruritic, painful/burning, fever, arthralgias
Drugs, infections, connective tissue diseases, and neoplasms
Usually self‐limited, rest, elevation, compression, NSAIDs, anti‐histamines, corticosteroids, colchicine, dapsone, and immunosupressants
Henoch–Schönlein purpura
Palpable purpura on extensors and buttocks, pts 4–7 yrs old polyarthralgia (75%), GI bleeding, fever, hematuria, edema, renal dysfunction, pulmonary hemorrhage, and headache
1–2 weeks after respiratory infection, allergens/food, drugs; usually unknown
Primarily supportive. corticosteroids, other immunosuppressants, dapsone, factor XII
Acute hemorrhagic edema of infancy
Large, annular, purpuric plaques and edema on face, ears, extremities, usually in patients <2 yo
Infections (especially respiratory), drugs, vaccines; usually unknown
Self‐resolving
Urticarial vasculitis
Painful >pruritic, lasts >24 h, post‐inflammatory hyperpigmentation, +/– bullae, systemic dz in hypocomplementemic version (anti‐C1q precipitin, F > M, ocular, angioedema, COPD), F > M
Autoimmune/CTD (30% of Sjogren,20% of SLE pts), drugs (serum sickness), infections (HBV, HCV, EBV), neoplasms, Schnitzler syndrome
Oral corticosteroids, antimalarials, dapsone, colchicine, anti‐histamines, and NSAIDs
Hyperimmuno‐globulinemia D syndrome
Periodic fever, arthralgia, GI sxs, LAN, erythematous macules/papules/nodules/urticaria on extremities, onset <10 yo, ↑ IgD and IgA levels
AR; Mevalonate kinase deficiency
NSAIDs, anti‐IL‐1 Ab, and corticosteroids
Familial mediterranean fever
Periodic fever, arthritis, serositis, erysipelas‐like rash on legs, myalgias, AA amyloidosis, renal failure, PID sxs; unlike Hyper‐IgD, no LAN and nl IgD level
AR; Pyrin deficiency
Colchicine, anti‐IL‐1
Erythema elevatum Diutinum
Yellow/brown/red papules, plaques, and nodules over joints
Various associations: hematologic diseases, HIV, IBD, CTD, and streptococcal infections
Dapsone, niacinamide, and topical/intralesional corticosteroids
Granuloma faciale
Brown/red plaques on face
Middle‐aged, M > F, Caucasian
Unknown
Treatment‐resistent, intralesional steroids, dapsone, and surgery
Serum sickness
Fever, lymphadenopathy, arthralgias, urticaria, maculopapular, scarlatiniform, purpura, and myalgias
Type III hypersensitivity, commonly following streptokinase, IVIG, Abx (cefaclor, PCN, MCN, rifampin, and cefprozil)
Avoidance, anti‐histamines, anti‐pyretics, and corticosteroids
Medium (± small) vessel vasculitis
Polyarteritis nodosa (systemic)
SQ nodules on legs, livedo reticularis, “punched‐out” ulcers, digital gangrene, p‐ANCA positive, universal multisystemic involvement: myocardial/GI/renal infarction, polyneuritis, CNS, arthralgias, weight loss, HTN, (renal) microaneurysms, orchitis (esp. with HBV)
Various infections/inflammatory conditions: streptococcus, HBV, HCV, CMV, HIV, SLE, IBD, and hairy cell leukemia
Corticosteroids, cyclophosphamide
Polyarteritis nodosa (cutaneous)
SQ nodules, starburst pattern of livedo reticularis, mild fever, nerve and muscle involvement
As above (cPAN represents 10% but is most common form in children, more often strep)
Topical/intralesional steroids, PCN
Microscopic polyangiitis
Palpable purpura, ulcers, splinter hemorrhages, crescentic necrotizing segmental GN, fever, weight loss, myalgias, neuropathy, HTN, p‐ANCA (60%); c‐ANCA (40%)
Corticosteroids, cyclophosphamide
Granulomatosis with polyangiitis (formerly Wegener’s)
Respiratory, renal, sinus, ocular, otologic, CNS, cardiac, joints, nasal nodules/ulcers/saddle nose, pulmonary infiltrates/nodules, SQ nodules, and c‐ANCA (85%)
Unknown – distinguish from lymphomatoid granulomatosis – severe EBV+ angioinvasive B‐cell lymphoma of skin and lungs
Corticosteroids, cyclophosphamide (treat staph infection and nasal carriage to minimize relapse)
Churg–Strauss syndrome (Allergic granulomatosis)
Asthma, sinusitis, allergic rhinitis, eosinophilia, arthritis, myositis, CHF, renal/HTN, mononeuritis multiplex, palpable purpura, infi ltrated nodules, p‐ANCA (60%)
Vaccination, leukotriene inhibitors, desensitization therapy, rapid steroid taper
Corticosteroids, cyclophosphamide
Large vessel vasculitis
Giant cell arteritis (temporal)
Tender, temporal artery, polymyalgia rheumatica, unilateral HA, jaw claudication, blindness, F > M, Northern European
Unknown
Corticosteroids
Takayasu arteritis
Constitutional sxs, pulselessness, signs/sxs of ischemia, EN‐like nodules, and pyoderma gangrenosum‐like lesions
Associations: RA, other CTD
Corticosteroids, cyclophosphamide, surgical revascularization
Cryoglobulinemia
Cryoglobulinemia type
Monoclonal or polyclonal
Immunoglobulins
Diseases
1 (“Simple/Single”)
Single monoclonal
IgM > IgG > IgA or light chain
Associations: Lymphoproliferative disorders: lymphoma, CLL, myeloma, and Waldenstrom macroglobulinemia
Manifestations: Retiform necrotic lesions, acrocyanosis, Raynaud phenomenon, cold urticaria, livedo reticularis, retinal hemorrhage, and arterial thrombosis
2 (“Mixed”)
Monoclonal and polyclonal
Monoclonal IgM (RF) complexed to polyclonal IgG
Associations: HCV > other autoimmune (Sjögren, SLE, and RA), infections (CMV, EBV, HIV, HBV, and HAV), and lymphoproliferative disorders
Manifestations: LCV with palpable purpura, arthralgias/arthritis involving PIPs, MCPs, knees and ankles, diffuse GN
3 (“Mixed”)
Polyclonal
IgG and/or IgM
Associations: HCV, other autoimmune (Sjögren, SLE, and RA), infections (CMV, EBV, HIV, HBV, and HAV), and lymphoproliferative disorders
Manifestations: LCV with palpable purpura, arthralgias/arthritis PIP, MCP, knees and ankles, and diffuse GN
Bullous Disorders
Intracorneal/subcorneal
Intraepidermal
Suprabasilar
Subepidermal with little inflammation
Subepidermal with lymphocytes
Subepidermal with eosinophils
Subepidermal with neutrophils
Subepidermal with mast cells
Epidermolysis bullosa
Major bullous diseases – clinicopathologic findings
Disease
Manifestation
Antigen(s)
Size (kD)
Path
DIF
Rx
Pemphigus foliaceus
Crusted, scaly erosions, seborrheic distribution, positive Nikolsky, non‐mucosal
Dsg 1
Plakoglobin
160
85
Acantholysis in upper epidermis, split in SG or right below SC
Intercellular IgG/C3, often superficial, may be thoughout epidermis
Topical steroids if mild, systemics similar to PV if generalized
Pemphigus vegetans
Flaccid bullae, erosions, fungoid vegatations, intertriginous, head, mucous membrane, two subtypes: Neumann – severe, Hallopeau – mild
Dsg 3
Dsg 1
Plakoglobin
130
160
85
Like PF
Like PF
Like PF
Pemphigus vulgaris
Drug‐induced (usually PF‐like): penicillamine, IL‐2, PCN, thiopurine, rifampin, ACE‐I
Flaccid bullae, mucous membrane, + Nikolsky, + Asboe–Hansen
Dsg 3–100%
Dsg 1–~50%
Plakoglobin
130
160
85
Suprabasilar acantholysis can follow hair, + tombstones
Intercellular IgG (also C3, IgM, and IgA) thoughout epidermis.
Follow progression with IIF (Dsg 3) (monkey esophagus)
Prednisone, azathioprine, cyclophosphamide, mycophenolate mofetil, and CSA
IgA pemphigus
Flaccid vesicles, superficial pustules in annular/serpentine patterns, trunk (axilla, groin), proximal extremities
SPD variant – Desmocollin 1; IEN variant – Dsg 1/3
105, 115
Pustules: subcorneal or suprabasilar, no acantholysis, PMNs
IgA in upper epidermis (intercellular), no IgG
Dapsone, sulfapyridine, etretinate, UV, and steroids
Pemphigus erythematosus
(Senear–Usher)
Erythematous, crusted, erosions, often malar, originally PE = PV + LE
Dsg 1
Plakoglobin
160
85
Like PF
Intercellular and DEJ IgG/C3+ lupus band sometimes
Prednisone
Paraneoplastic pemphigus
Associations: NHL, CLL, Castleman, sarcoma, and thymoma
Bullae, erosions, EM‐like, lichenoid, SJ‐like in mucous membranes
Plectin
Desmoplakin 1
BPAg1
Envoplakin
Desmoplakin 2
Periplakin
Dsg 1,3
500
250
230
210
210
190
170
160, 130
Suprabasilar acantholysis, dyskeratotic keratinocytes, sometimes basal layer degeneration/band‐like infiltrate
Intercellular IgG/C3 in
epidermis and at BMZ
IIF: IgG rat bladder
Treat‐associated neoplasm
May die from bronchiolitis obliterans
Epidermolysis bullosa acquisita
Associations: myeloma, colitis, DM2, leukemia, lymphoma, amyloid, and cancer
Fragile skin, blisters with trauma, atrophic scars, milia, and nail dystrophy
Col VII (also an antigen in bullous LE)
290/145
Noninflammatory subepidermal bullae, PMN > Eos
IgG/C3 linear BMZ
IIF anti‐BMZ
Salt split skin: immunoreactants on dermal side, type IV collagen on roof
Immunosuppression, wound care
Bullous pemphigoid
Drug‐induced: lasix, PCN, ACE‐I, sulfasalzine, and nalidixic acid
Large, tense bullae on trunk and extremities
BPAg1
BPAg2
BPAg2 worse prognosis.
230
180
Subepidermal bullae, eosinophils in superficial dermis (more likely acral in infants)
Linear IgG/C3 at BMZ
Salt split skin: immunoreactants on epidermal side, type IV collagen on base
Topical steroids, prednisone, MTX, mycophenolate mofetil, azathioprine, nicotinamide, TCN, sulfapyridine, dapsone
Herpes gestationis/gestational pemphigoid
Associations: HLA‐DR 3,4, B8
Pruritic, urticarial plaques on trunk, starts near umbilicus, flares with delivery/OCP, increased risk of prematurity/SGA, 10% of newborns with skin lesions
BPAg1
BPAg2
230
180
Subepidermal bullae, eosinophils, perivascular infiltrate
Linear C3 ± IgG at BMZ
IIF: anti‐BMZ IgG by complement‐added IIF.
Topical/oral steroids
Dermatitis herpetiformis
Grouped, pruritic papules and vesicles on extensors,
HLA‐B8, DR3, and DQ2
Endomysial Ag (tissue transglutaminase)
Anti‐gliadin
—
Subepidermal bullae, PMNs in dermal papillae
Granular IgA ± C3 (tips of papillae)
Gluten‐free diet, dapsone, sulfapyridine, TCN, nicotinamide, and colchicine
Linear IgA
Drug‐induced: vancomycin, lithium, amiodarone, ACE‐I, PCN, PUVA, lasix, IL‐2, oxaprozin, IFN‐γ, dilantin, diclofenac, and glibenclamide
DH‐like vesicles (crown of jewels), BP‐like bullae, 50% mucous membrane involvement, children: self‐limited
Ladinin
LAD‐1
BPAg1
BPAg2
Col VII
97
120
230
180
290/145
Subepidermal bullae, PMNs in dermal papillae ± Eos
Linear IgA at BMZ, maybe IgG, no C3
Dapsone, steroids, TCN, nicotinamide, IVIg, and colchicine
Cicatricial pemphigoid (benign mucosal pemphigoid)
Drug‐induced: penicillamine, clonidine
Primarily mucous membrane, vesicles, erosions, ulcers, scars, erosive gingivitis, and chronic
BPAg1
BPAg2
Laminin‐6
Epiligrin (Lam‐5)
Integrin β4
230
180
165, 220, 200
165, 140, 105
200
Like BP plus scarring in upper dermis
C3/IgG at BMZ in 80%;
IIF+ in 20%, usually IgG
Topical steroids, dapsone, cyclophosphamide, oral steroids, and surgery.
Complement
Complement type
Action
C1q
Binds antibody, activates C1r
C1r
Activates C1s
C1s
Cleaves C2 and C4
C2
Cleaves C5 and C3
C3a
Basophil and mast cell activation
C3b
Opsonin, component at which classical and alternative pathways converge
C4a
Basophil and mast cell activation
C4b
Opsonin
C5a
Basophil and mast cell activation
C5b, 6, 7, 8, 9
Membrane attack complex
C5, 6, 7
PMN chemotaxis
C5b
Basophil chemotaxis
Angioedema and complement levels
C1
C1 INH
C2
C3
C4
HAE – 1
Nl
↓
↓
Nl
↓
HAE – 2
Nl
Nl/↑ (but nonfunctional)
↓
Nl
↓
HAE – 3*
Nl
Nl
Nl
Nl
Nl
AAE – 1**
↓
↓
↓
Nl/↓
↓
AAE – 2***
↓
↓
↓
Nl/↓
↓
ACEI‐induced
Nl
Nl
Nl
Nl
Nl
Complement deficiencies
Complement deficiency
Disease
Early classical pathway (C1, C4, C2)
SLE without ANA, increased infections (encapsulated organisms)
C1 esterase
HAE
Decreased C1q
SCID
C2
Most common complement deficiency, SLE (sometimes HSP, JRA)
C3
Infections, SLE, partial lipodystrophy, Leiner disease
C4
SLE with PPK
C3, C4, or C5
Leiner disease (diarrhea, wasting, and seborrheic dermatitis)
C5–9
Recurrent Neisseria infections
GVHD (Graft vs. Host Disease)
HLA associations
Disease
Associated HLA(s)
Abacavir‐induced hypersensitivity syndrome
B*5701
Actinic prurigo
DR4 (DRB1*0401), DRB1*0407
Acute generalized erythematous pustulosis
B5, DR11 and DQ3
Allopurinol‐induced SJS/TEN
– Han Chinese
B*5801
Alopecia areata
– all types
– HLA‐DQB1*0301 (DQ7), HLA‐DQB1*03 (DQ3), and HLA‐DRB1*1104 (DR11)
– severe alopecia totalis/universalis
– DRB1*0401 (DR4) and HLA‐DQB1*0301 (DQ7)
Behçet’s disease
B51
Bullous pemphigoid
– Caucasians
– DQB1*0301
– Japanese
– DRB1*04, DRB1*1101, and DQB1*0302
Carbamazepine‐induced SJS/TEN
– Asians and East Indians
– B*1502
– Europeans
– A*3101
Chronic urticarial
DR4, DQ8
Dermatitis herpetiformis
DQ2, B8
Dermatomyositis
– Juvenile
– DR3, B8
– with anti‐JO antibodies
– DR52
– with anti‐Mi‐2 antibodies
– DR7, DRw53
– adults with dermatomyositis overlap
– B14, B40
– Japanese with juvenile dermatomyositis
– DRB1*15021
Epidermolysis bullosa aquisita
– Caucasians and African Americans
– DRB1*1501, DR5
– Koreans
– DRB1*13
Erythema dyschromium perstans
Mexican patients
DR4
Erythema multiforme
DQw3, DRw53, and Aw33
Generalized granuloma annulare
Bw35
Granulomatosis with polyangiitis
(formerly Wegener’s)
DPB1*0401
Henoch–Schonlein purpura
With renal disease
B35
Juvenile idiopathic arthritis
– Type II oligo/pauciarticular arthritis
– B27
– Enthesitis‐related arthritis
– B27
Leprosy
– Lepromatous form
– DQ1
– Tuberculoid form
– DR2, DR3
Lichen planus
– Oral and cutaneous
– DR1
– Oral
– English patients
– B27, B51, and Bw57
– Japanese and Chinese patients
– DR9
– HCV patients
– DR6
Mixed connective tissue disease
DR4, DR1, and DR2
Mucous membrane pemphigoid
DQw7
Pemphigoid gestationis
DR3, DR4
Pemphigus vulgaris
– Caucasians
– Japanese
– DRB1*0402, DRB1*1401 and DQB1*0302
– DRB1*14 and DQB1*0503
Psoriasis
– Early onset
Cw6 (also in late‐onset), DRB1*0701/2
Relapsing polychondritis
DR4
– Negatively associated w/ organ involvement
DR6
Rheumatoid arthritis
DR1, DR4, and DRB1
Sacroiliitis
– Psoriasis
– Crohns
– UC
– SAPHO
– Reactive arthritis
B27
Sarcoidosis
1, B8, DR3, DRB1, and DQB1
Stevens–Johnson syndrome
With ocular complications
DQB1*0601
Still’s disease, Adult‐onset
B14, B17, B18, B35, Bw35, Cw4, DR2, DR7, DR4, and Dw6
Subacute cutaneous lupus erythematosus
B8, DR3
Systemic lupus erythematosus
A1, B8, and DR3
Th profiles
Th profile
Cytokines
Associated diseases
Th1
IL‐2, IFN‐γ, IL‐12
Tuberculoid leprosy, Cutaneous leishmaniasis, Erythema nodosum, Sarcoidosis, Behcet, and MF
Th2
IL‐4, IL‐5, IL‐6, IL‐10, IL‐9, IL‐13
Atopic dermatitis, Lepromatous leprosy, Disseminated leishmaniasis, and Sezary
Th17*
IL‐6, IL‐15, IL‐17, IL‐21, IL‐22, IL‐23, TGFβ
Psoriasis, ACD, and Hyper‐IgE
T regulatory
IL‐10 or TGFβ (also CD25+ and FOXP3+)
IPEX
SPECIAL SITES: GLANDS, NAIL, BONE, MUCOSA
Glands
Glands
Apocrine
Eccrine
Sebaceous
Derivation
Ectodermal (~weeks 16–24)
Ectodermal (~week 14)
Ectodermal (~week 14)
Secretion
Decapitation
Merocrine
Holocrine
Innervation
Sympathetic adrenergic
Sympathetic cholinergic and cholinergic
Androgenic hormones (not innervated)
Purpose
Pheromones
Temperature regulation
Lubricate, waterproof
Locations
Axillary, breast (mammary), external ear (ceruminous), anogenital, eyelid (Moll)
Nevus sebaceous
Widespread (especially soles) excluding vermilion border, labia minora, glans, nail beds, and inner prepuce
Everywhere except palms and soles
Associated with hair follicles except on mucosa
Montgomery tubercles – nipples, areola
Meibomian – deep eyelid; granuloma
Glands of Zeis – superficial eyelid
Tyson – foreskin, labia minora
Fordyce spots – vermilion, buccal
Secretion contents
Fatty acids, cholesterol, triglycerides, squalene, androgens, ammonia, iron, carbohydrates, antimicrobial peptides
NaCl, potassium, bicarbonate, calcium, glucose, lactate, urea, pyruvate, glucose, ammonia, enzymes, cytokins, and Ig’s
Ceramides, triglycerides, free fatty acids, squalene, sterol and wax esters, free sterols
Stains *
GCDFP, EMA, CEA, keratins
CEA, S100, EMA, keratins (CAM 5.2, AE1)
EMA, CK15, lipid stains
Nonneoplastic conditions
Nail terminology
Sign
Definition/due to
Associated conditions
Nail plate/nail shape abnormalities
Anonychia
Absence of nail plate or nail unit
—
Angel wing deformity
Central portion of nail is raised and lateral portions are depressed. Due to nail plate thinning
Lichen planus
Beau line
Transverse (horizontal) ridges affecting all nail plates due to intermittent injury to the nail matrix
Acute systemic illness
Brachyonychia
Short, wide nails (racquet nails)
Rubinstein–Taybi
Clubbing
Bulbous fusiform enlargement of the distal portion of the digit with exaggerated curvature of the nail and flattening of the angle between the proximal nail fold and nail plate
Idiopathic (pahcydermoperiostosis, familial clubbing, hypertrophic osteoarthropathy); Secondary (systemic disease)
Koilonychia
Concave, spoon‐shaped nails
Normal variant, iron deficiency anemia (Plummer–Vinson associated with esophageal webbing), diabetes, protein deficiency, connective tissue disease, and acitretin
Habit tic deformity
Longitudinal furrow with multiple transverse parallel lines in the center
Habitual picking of the proximal nail fold, most common the thumb
Longitudinal groove
Central longitudinal groove/median canaliform dystrophy
Growth at the nail matrix such as myxoid cyst or wart
Longitudinal splitting
Extension of ridging
Lichen planus, psoriasis, darier, and fungal infection
Median nail (canaliform) dystrophy
Central longitudinal ridge with feathering, like branches of a Christmas tree
Unknown, trauma may play a role
Onychocryptosis
Ingrown nail with granuloma
Aggravated by oral retinoids
Onychorrhexis
Longitudinal ridging
Lichen planus, psoriasis, darier, and fungal infection
Onychogryphosis
Thick curved nail plate (ram’s horn)
Aging, psoriasis, trauma, and ill‐fitting shoes
Onychomadesis
Transverse full thickness break in the nail from temporary growth arrest of the nail plate (unlike Beau line – partial thickness)
Viral infection such as hand–foot–mouth disease
Onychauxis
Thick nail plate
Psoriasis, trauma, and fungal nail infection
Onychoschizia
Splitting/brittle nail
Water damage
Pincer nail
Transverse over‐curvature of the nail plate, sometimes causing pain at the lateral nail plates curving into the nail bed/fold
Psoriasis, SLE, Kawasaki disease, cancer, and paronychia congenita
Pitting
Inflammatory condition affecting the nail matrix or bed
Alopecia areata, eczema, and psoriasis
Trachyonychia
Rough opaque nails
Lichen planus, Twenty nail dystrophy (if all nails affected), alopecia areata, atopical dermatitis, and psoriasis
Transverse ridging
—
Eczema, paronychia, and psoriasis
Nail discoloration
Blue nail
—
Wilson disease (blue lunula), argyria, oral medications (minocycline, AZT, HIV, antimalarials, and busulfan)
Green nail
Striking blue‐green color to 1 or 2 nails
Pseudomonas or candida infection
Yellow nail syndrome
Yellow, hard, hypercurved (classic hump), thickened nail
Due to lymphatic obstruction associated with lymphedema, pleural effusion, and ascites. Biotin 10 mg qd and fluconazole may be helpful
Yellow nail
Yellow discoloration
Funal nail infection, yellow nail syndrome, and quinacrine (fluorescent on black light)
Oil drop sign
Salmon colored “oil” spots in the nail bed. Caused by exudation of a serum glycoprotein in psoriasis
Psorasis
Orange streak
Orangish/yellow patch
Dermatophytoma (dermatophyte abscess)
Brown nail
—
Staining (nicotine, potassium permanganate, nail varnish, and podophyllin); chemotherapy, hyddroxyurea
Leukonychia (white nail)
White spots or white discoloration (see also Mee lines and Muehrcke lines)
Trauma (especially to the cuticle that does not follow contour of the matrix), superficial onychomycosis (T. mentagrophytes in immunocompetent; T. rubrum in HIV and kids)
Transverse leukonychia
Multiple parallel white lines
Manicuring, associated with beau lines
Mee lines
Partial leukonychia. Transverse white bands on several nails (follows the contour of lunula because of matrix growth) These grow out
Arsenic, thallium, or other heavy metal poisoning, systemic disease, chemotherapy, thallium and antimony intoxication, and etretinate therapy
Muehrcke lines
Apparent leukoychia – Double band
Disappears with digital pressure
Hypoalbuminemia, correlates with serum albumin below 2.2 g/100 ml
Half and half nail (Lindsay nail)
Apparent leukonychia: white proximal nail, brown or pink distal nail
Renal failure
Terry nail
White proximal nail (about 2/3), reddened distal nail
Liver cirrhosis
Onycholysis
Lifting of the distal nail plate. Appears white or yellow.
Idiopathic, trauma, contact dermatitis, photoonycholysis (tetracycline, psoralens) and drug reaction (5FU, doxorubicin, captopril, etretinate, isotretinoin, indomethacin, isoniazid, and griseofulvin). Partial onycholysis can occur in psoriasis, thyrotoxicosis, and candida infection.
Melanonychia striata/Longitudinal melanonychia
Longitudinal hyperpigmented band(s) extending from the proximal nail plate to the distal end of the nail plate
Normal physiologic variant, trauma, pregnancy, Addison disease, post inflammatory hyperpigmentation, Laugier–Hunziker, and Peutz–Jeghers. Can be associated with doxorubicin, 5FU, AZT, and psoralen. Can occur in benign melanocytic nevi and malignant melanoma (Hutchinson sign – extension of the hyperpigmentation through the lunula to the proximal nail fold and cuticle)
Candida can sometimes cause candida black melanocyhia at the lateral edge. Exposure to hydroquinone and vitamin C can cause multiple melanonychia that scrapes off
Erythronychia (Red nail)
Longitudinal thin red/brown line beneath the nail plate
Splinter hemorrhage (Red nail)
Multiple longitudinal thin red/brown lines beneath the nail plate
Multiple nails = inflammation/systemic disease; SLE, rheumatoid arthritis, antiphospholipoid syndorome, malignancy, OCP use, pregnancy, psoriasis, and trauma
Abnormalities of the cuticle, lunula, and nail fold
Pterygium
V formation scarring from the proximal nail outward
Due to scarring in the nail matrix. Seen in lichen planus, Stevens–Johnson, after trauma.
Ragged cuticle
—
Connective tissue disease, parakeratosis pustulosa
Blue lunula
—
Wilson disease (dark blue); Diabetes (pale blue)
Red lunula
—
Cardiovascular disease, collagen vascular disease, and hematologic malignancy
Absent lunula
—
Anemia or malnutrition
Nail fold telangiectasia
Dilated capillaries at the ponychium (just proximal to the cuticle)
Connective tissue disease (SLE, rheumatoid arthritis, dermatomyositis, and scleroderma)
Disorders or drugs associated with nail, bone, or ocular findings
Ocular
Skeletal/oral
Nail
5‐FU, AZT, Phenophthalein, antimalarials, Hydroxyurea, MCN
—
—
Blue lunulae (also argyria, Wilson, Hgb M dz)
Acitretin
—
—
Koilonychia, onychocryptosis (ingrown/unguis incarnatus, granuloma)
Acne fulminans
—
Osteolytic lesions (clavicle, sternum, long bones, ilium)
—
Albright hereditary osteodystrophy
—
Short stature, brachydactyly, subcutaneous ossifications
—
Alkaptonuria
Osler sign (blue/gray slerae)
Arthritis, blue/gray ear cartilage, calcified cartilage
—
Alezzandrini
Unilateral retinitis pigmentosa, retinal detachment
—
—
Alopecia areata
Asx punctate lens opacities
—
Pitting, trachyonychia, red spotted lunulae
Antimalarials
Retinopathy
—
Blue lunulae
Apert
Hypertelorism, exophthalmos
Craniosynostosis
Brittle nails, fusion of nails
Argyria
Blue/gray sclera
Blue/gray gums
Azure lunulae
Arsenic
—
Garlic breath, intra‐abdominal radio‐opacities (acute)
Mees lines
Ataxia‐Telangiectasia (Louis–Bar)
Bulbar telangiectasia, strabismus, nystagmus
—
—
Behçet
Retinal vasculitis, uveitis, hypopyon, optic disc hyperemia, macular edema
Arthritis, oral ulcers
—
Buschke–Ollendorff
—
Osteopoikolosis
—
Carbon monoxide poisoning, Polycythemia, CTD, CHF
—
—
Red lunulae
CHIME
Retinal colobomas
—
—
Cicatricial pemphigoid
Conjunctivitis, symblepharon, synechiae, ankyloblepharon
Oral ulcers, hoarseness, dysphagia
—
Cirrhosis, CHF
—
—
Terry nails
Cholesterol emboli
Hollenhorst plaque
—
—
Cockayne
Salt and pepper retinal pigmentary degeneration, optic atrophy, cataracts, strabismus, nystagmus, sunken eyes
Dwarfism, dental caries, osteoporosis, overcrowded mouth
—
Coffin–Siris
Bushy eyebrows
Hypoplastic/absent fifth distal phalanges, microcephaly
Hypoplastic/absent fifth nail
Congenital erythropoietic porphyria
Conjunctivitis, scleromalacia perforans
Erythrodontia, acro‐osteolysis, osteoporosis
Nail dystrophy
Congenital syphilis
Keratitis
Osteochondritis, saddle nose, mulberry molars, Hutchinson teeth, saber shins
—
Connective tissue disease, Trauma
—
Pterygium inversum unguis
—
Conradi–Hünermann syndrome
Striated cataracts, microphthalmus, optic nerve atrophy
Asymmetric limb shortening, chondrodysplasia punctata – stippled epiphyses (also in CHILD)
—
Cooks syndrome
—
Absent/hypoplastic distal phalanges, brachydactyly fifth finger
Anonychia/onychodystrophy
Darier–White
—
—
Longitudinal red and white bands and ridging, V‐shaped notches, subungual hyperkeratosis
Dermochondrocorneal dystrophy (Francois)
Corneal dystrophy, central opacities
Acral osteochondrodystrophy, contractures, subluxations, gingival hyperplasia
—
Drug (azidothymidine, tetracycline), Ethnicity, Laugier–Hunziker, Peutz–Jeghers
—
—
Longitudinal melanonychia
Dyskeratosis congenita
Blepharitis, conjunctivitis, epiphora
Dental caries, loss of teeth, premalignant leukoplakia, dysphagia
Longitudinal ridging, thinning, pterygium
Ehlers–Danlos VI
Fragile sclerae/cornea, keratoconus, hemorrhage, retinal detachment, blue sclerae, angioid streaks
Kyphoscoliosis
—
Ehlers–Danlos VIII
—
Periodontitis, loss of teeth
—
Ehlers–Danlos IX
—
Occipital horns, elbow and wrist defects
—
Endocarditis, trauma, trichinosis, cirrhosis, vasculitis
—
—
Splinter hemorrhages
Epidermal vevus syndrome
Lipodermoids, colobomas, choristomas
Kyphoscoliosis, abnormal skull shape, limb hypertrophy/asymmetry, rickets
—
Fabry disease
Circular corneal opacities (cornea verticillata), tortuous vasculature, spoke‐like cataracts
Oral angiokeratoma (tongue), osteoporosis
—
Fanconi anemia
Strabismus, retinal hemorrhages
Radius and thumb defects
—
Fever, stress, meds (chemo)
—
—
Beau lines
Gardner
Congenital hypertrophy of retinal pigmented epithelium
Osteomas, dental abnormalities
—
Gaucher
Pingueculae
Erlenmeyer flask deformity, osteopenia, osteonecrosis
—
Goldenhar (Facioauriculovertebral sequence)
Epibulbar choristomas, blepharoptosis or narrow palpebral fissures, eyelid colobomas, lacrimal drainage system anomalies
Ipsilateral mandibular hypoplasia, ear anomalies, vertebral anomalies
—
Goltz
Retinal colobomas, microphthalmia, nystagmus, strabismus
Osteopathia striata, lobster claw deformity, cleft lip/palate, hypo/oligodontia, oral papilloma, enamel hypoplasia
—
Gorlin
Cataracts, strabismus, iris colobomas
Odontogenic cysts, fused/bifid ribs, spina bifida occulta, kyphoscoliosis, calcified falx cerebri, frontal bossing
—
Hallermann–Streiff syndrome
Microopthalmia, congenital cataracts, strabismus
Bird‐like facies, natal teeth, hypodontia
—
Hemochromatosis
Angioid streaks
—
Koilonychia
Homocystinuria
Ectopia lentis (downward)
Marfanoid habitus, genu valgum, osteoporosis
—
Huriez
—
Scleroatrophy of hands, sclerodactyly, lip telangiectasia
Hypoplasia, ridging, white, clubbing
Hyperimmunoglobulin E syndrome
—
Osteopenia, fractures, scoliosis, hyperextensible joints, candidiasis
Chronic candidiasis
Hypoalbuminemia
—
—
Muehrcke lines
HSV, varicella
Dendritis, keratitis
—
—
Incontinentia pigmenti (Bloch‐Sulzberger)
Strabismus, cataracts, optic nerve atrophy, retinal vascular changes, detached retina, retinal/iris colobomas
Peg/conical teeth, partial adontia, late dentition
Nail dystrophy, grooving, painful subungual dyskeratotic tumors
Iron deficiency, Syphilis, Thyroid Dz
—
—
Koilonychia
Iso‐Kikuchi
—
Index finger hypoplasia, brachydactyly
Hypoplastic index finger nail
JXG
Ocular JXG, hyphema, glaucoma
—
—
KID
Keratoconjunctivitis, blepharitis, photophobia, corneal defects
—
Nail dystrophy
Kindler
—
Cicatricial pseudosyndactyly (between MCP and PIP), leukoplakia, caries
Nail dystrophy
Lamellar Ichthyosis
Ectropion, corneal damage
Phalangeal reabsorption
—
LCH: Hand‐Schuller‐Christian
Exophthalmos
Bone lesions (esp. cranium)
—
LEOPARD
Hypertelorism
—
—
Leprosy
Madarosis, lagophthalmos, keratitis, episcleritis, corneal anesthesia, blindness
Digital resorption, malaligned fractures, diaphyseal whittling, saddle nose
Longitudinal melanonychia, longitudinal ridging, subungual hyperkeratosis, rudimentary nail
Lichen planus
—
—
Pterygium
Linear morphea
—
Melorheostosis (of Leri; “flowing candle wax”)
—
Lipoid proteinosis (Urbach‐Wiethe)
Eyelid beading/moniliform blepharosis
Calcifications in hippocampus (suprasellar, “bean‐shaped”), thick tongue, hoarseness
—
Mafucci
—
Enchondromas, chondrosarcoma
—
Marfan
Ectopia lentis (upward)
Marfanoid habitus
—
McCune–Albright
—
Polyostotic fibrous dysplasia
—
MEN IIb
Conjunctival neuroma
Plexiform neuromas (oral mucosa, tongue), nodular lips, marfanoid habitus
—
MEN III
—
Marfanoid habitus
—
Menkes
Blue irides, strabismus, aberrant eyelashes, iris stromal hypoplasia
Wormian bones of skull, metaphyseal spurring of long bones
—
Multicentric reticulohistiocytosis
—
Mutilating arthritis
—
Myxoid cyst, verruca vulgaris
—
—
Median canaliform dystrophy
Naegeli–Franceschetti–Jadassohn
Periocular hyperpigmentation
Syndrome enamel defects, perioral hyperpigmentation
Malaligned great toenails
Nail–Patella
Lester iris, heterochromia irides
Patella aplasia, posterior iliac horns, elbow arthrodysplasia
Triangular lunulae, micro/anonychia
Necrobiotic xanthogranuloma
Scleritis, episcleritis
—
—
NF‐1
Lisch nodules, congenital glaucoma, optic glioma
Sphenoid wing dysplasia
—
NF‐2
Cataracts, retinal hamartomas
—
—
Nicotine, chemotherapy, potassium permanganate, podophyllin, hydroxyurea (streaks)
—
—
Brown nails
Niemann–Pick
Cherry red spots, macular haloes
—
—
Noonan
Hypertelorism, ptosis, epicanthic folds, downward palpebral fissures, epicanthic folds, refractive errors, strabismus, amblyopia
Pectus carinatum superiorly, pectus excavatum inferiorly, scoliosis, short stature, cubitus valgus, joint hyperextensibility
—
Old age
—
—
Diminished or absent lunulae, longitudinal ridging, onychogryphosis
Olmsted
Corneal anomalies
Osteoporosis, joint laxity, leukoplakia, periorifical keratotic plaques
Nail dystrophy
Orofaciodigital 1
Colobomas
Bifid tongue, accessory frenulae, lip nodules/pseudoclefting, supernumerary teeth, frontal bossing, syndactyly
—
Osteogenesis imperfecta
Blue sclera
Brittle bones
—
Pachyonychia congenita
Corneal dystrophy
Oral leukokeratosis, natal teeth
Thickened nails, pincer nails, paronychia
Papillon–Lefévre
—
Dural calcifications, periodonitis, gingivitis (+ acro‐osteolysis and onychogryphosis in Haim‐Munk)
—
Phenylketonuria
Blue irides
Osteopenia
—
Porphyria cutanea tarda
—
—
Photo‐onycholysis
Progeria
—
Delayed/abnormal dentition, high‐pitched voice, acro‐osteolysis, short stature, osteoporosis, persistent open fontanelles
—
Pseudomonas (Pyocyanin)
—
—
Green nails
Psoriasis
—
—
Nail pits, oil spots
PXE (Gronblad–Strandberg)
Angioid streaks (also Paget’s Dz of bone, sickle cell, thalassemia, Pb poisoning, HFE, ED6)
Oral yellow papules
—
Refsum
Salt and pepper retinitis pigmentosa
Epiphyseal dysplasia
—
Relapsing polychondritis
Conjunctivitis, scleritis, uveitis, corneal ulceration, optic neuritis
Arthritis (truncal), aphthosis
—
Renal disease
—
—
Lindsay nails
Retinoids, indinavir, and estrogen
—
Isotretinoin – DISH‐like hyperostotic changes (bones spurs, calcified tendons, and ligaments)
Pyogenic granuloma
Richner–Hanhart
Pseudoherpetic keratitis
Tongue leukokeratosis
—
Rothmund–Thomson
Cataracts
Anomalies of radius and hands, hypodontia
Nail dystrophy
Rubinstein–Taybi
Long eyelashes, thick eyebrows, strabismus, cataracts
Broad thumb‐great toe, clinodactyly of fourth toe and 4th–5th fingers, short stature
Racquet nails
SAPHO
—
Osteomyelitis
—
Schnitzler
—
Bone/joint pain (iliac/tibia), hyperostosis, osteosclerosis
—
Schopf–Schulz–Passarge
Eyelid hidrocystomas
Hypodontia
Nail hypoplasia, dystrophy
Sjögren–Larsson
Retinitis pigmentosa, glistening dots
Short stature
—
Sturge–Weber
Glaucoma, retinal malformations
Tram‐track calcifications (skull X‐ray)
—
Sweet syndrome
Conjunctivitis, episcleritis, iridocyclitis
Arthritis, arthralgias
—
Tricho‐dento‐osseus
—
Caries, periodontitis, small teeth, enamel defects, tall stature, frontal bossing
Brittle nails
Trichorhinophalangeal
—
Cone‐shaped epiphyses, shortened phalanges and metacarpals, thin upper lip
Nail dystrophy
Trichothiodystrophy
Cataract, conjunctivitis, nystagmus
Osteosclerosis, short stature
Koiloynchia, ridging, splitting, leukonychia
Tuberous sclerosis
Retinal hamartomas (mulberry appearing), hypopigmented spots on iris
Dental pits, gingival fibromas, bone cysts, osteosclerosis
Koenen tumor
Vitamin A deficiency
Night blindness, unable to see in bright light, xerophthalmia, Bitot spots, keratomalacia
Growth retardation, excessive periosteal bone (decreased osteoclastic activity)
Brittle nails
Vitamin B2 (Riboflavin) deficiency (Oral–ocular–genital)
Eye redness, burning, fatigue, sandiness, dryness, photosensitivity to light, cataracts
Cheilosis, red sore tongue
—
Vitiligo
Uveitis, depigmented retina
—
—
Von Hippel Lindau
Retinal hemangioblastoma
—
—
Waardenburg
Dystopia canthorum, heterchromia irides
Caries, cleft lip/palate, scrotal tongue
—
Werner
Cataract, glaucoma
Sclerodactyly, osteoporosis, high‐pitched voice
—
Wilson
Kayser‐Fleischer ring
—
Blue lunulae
Witkop
—
Retained primary teeth
Nail dystrophy (toe>finger)
X‐linked chthyosis
Posterior comma‐shaped corneal opacities (Descemet’s membrane)
—
—
Yellow nail syndrome
—
—
Yellow nails, thick, slowed growth Yellow lunulae – consider insecticides/weed killers (dinitro‐orthocresol, diquat, and paraquat), tetracycline, smoking
Genital ulcers
Infection
Organism
Incubation
Presentation
Treatment
Notes
Chancroid
Haemophilus ducreyi
3–10 d
Painful, soft, ragged edges; tender, and unilateral LAN
Azithromycin, ceftriaxone, ciprofloxacin, and erythromycin
“School of fish” gram stain
Primary syphilis (Chancre)
Treponema pallidum
2–4 wk
Painless, indurated, sharp, and raised edges; bilateral and nontender LAN
Penicillin
Rubbery, “ham‐colored base”
Genital HSV
HSV
3–7 d
Painful, grouped
Antivirals
—
Lymphogranuloma venereum
Chlamydia trachomatis serovars L1–3
3–12 d
Painless, soft, tender LAN
Doxycycline
“Groove sign” – tender nodes around Poupart’s ligament
Donovanosis/granuloma inguinale
Calymmatobacterium/Klebsiella granulomatis
2–12 wk
Non‐ or mildly painful, beefy red, bleeding
TMP‐SMX, doxycycline, erythromycin, and ciprofloxacin
“Safety pin” Donovan bodies
INFECTION AND INFESTATIONS
Fungal Disease / Mycoses
Laboratory tests
Superficial mycoses
Cutaneous mycoses
Dermatophytes by sporulation characteristics
Trichophyton
Microsporum
Epidermophyton
Macroconidia
Shape
Wall
Rare
Cigar/pencilThin/smooth
ManySpindled/taperedThick/echinulate
Many, Grouped
Club/bluntThin/smooth
Microconidia
Many
Few
None
Dermatophytes by mode of transmission
Anthrophilic
Humans
T. rubrum, T. tonsurans, E. floccosum, T. concentricum, T. mentagrophytes var. interdigitale
Zoophilic
Animals
T. mentagrophytes var. mentagrophytes, M. canis, T. Verrucosum
Geographic
Soil
M. gypseum
Most common dermatophytes
Tinea corporis, tinea cruris, tinea mannum, tinea pedis
T. rubrum, T. mentagrophytes, E. floccosum
Tinea pedis
Moccasin: T. rubrum, E. floccosum
Vesicular: T. mentagrophytes var. mentagrophytes
Onychomycosis
Distal subungual: T. rubrum
Proximal white subungual (HIV): T. rubrum
White superficial: T. mentagrophytes (adults);
T. rubrum (children). Also molds: Aspergillus, Cephalosporium, Fusarium, Scopulariopsis
Tinea barbae
Usually zoophilic dermatophytes (especially T. mentagrophytes var. mentagrophytes and T. verrucosum) or T. rubrum
Tinea capitis
US: T. tonsurans > M. audouinii, M. canis
Europe: M. canis, M. audouinii
Favus: T. schoenleinii > T. violaceum, M. gypseum
Tinea imbricata/Tokelau
T. concentricum
Majocchi granuloma
Often T. rubrum > T. violaceum, T. tonsurans
Dermatophytes invading hair
Ectothrix
Fluorescent (pteridine)
M. canis, M. audouinii, M. distortum, M. ferrugineum, and M. gypseum
Nonfluorescent
T. mentagrophytes, T. rubrum, T. verrucosum, T. megninii, M. gypseum, and M. nanum
Endothrix (black dot)
T. rubrum, T. tonsurans, T. violaceum, T. gourvilli, T. yaoundie, T soudanense, and T. schoenleinii (fluoresces)
Fungal Disease ‐ Clinical Presentation and Management
Disease
Etiology
In Vivo/KOH (Tissue phase)
Culture (Mold phase)
Clinical
Tx
Subcutaneous mycoses
Sporotrichosis
Sporothrix schenckii
Cigar‐shaped budding yeast, Splendore–Hoeppli phenomenon
Hyphae with daisy sporulation
Florist, gardener, farmer‐ (rose thorn, splinter), Zoonotic (cats)
Sporotrichoid spread (fixed if prior exposure)
DDx for sporotrchoid spread: leishmaniasis, atypical mycobacteria, tularemia, nocardia, and furunculosis
Itraconazole, SSKI
Chromoblastomycosis
Fonsecaea (most common), Cladosporium, Phialophora, Rhinocladiella
Copper pennies/ Medlar bodies/Sclerotic bodies
—
Small pink warty papule → expands slowly to indurated verrucous plaques with surface black dots
Itraconazole, surgical excision
Phaeohyphomycosis
Exophiala jeanselmei, Wangiella dermatitidis, Alternaria, Bipolaris, Curvularia, Phialophora
Like chromo but with hyphae
—
Solitary subcutaneous draining abscess
Surgical excision, itraconazole
Lobomycosis (Keloidal Blastomycosis)
Loboa loboi (Lacazia loboi)
Lemon‐shaped cell chains with narrow intracellular bridges
Maltese crosses – polarized light
Not cultured
Bottle nose dolphins and rural men in Brazil
Confluent papules/ verrucous nodules that ulcerates/crusts
Fibrosis may resemble keloids
Surgical excision
Zygomycosis
Conidiobolus coronatus
—
—
Rhinofacial subcutaneous mass
—
Rhinosporidiosis (protozoan)
Rhinosporidium seeberi
Giant sporangia (raspberries)
Stains with mucicarmine
Not cultured
Stagnant water, endemic in India and Sri Lanka
Nasopharyngeal polyps – may obstruct breathing
Surgical excision
Protothecosis (algae)
Prototheca wickerhamii
Morula (soccer ball)
—
Olecranon bursitis
—
Actinomycotic mycetoma (bacterial)
Actinomadura pelletierii (red)
Actinomadura madurae (white)
Streptomyces (yellow)
Actinomyces israeli
Botryomycosis
Nocardia (white‐orange)
—
—
Volcano‐like ulcer and sinus tracts
Sulfur grains – yellow, white, red, or brown
Tissue swelling
Early bone and muscle invasion
Antimicrobial
Eumycotic mycetoma (fungal)
Pseudallescheria boydii (most common, white‐yellow)
Madurella grisea
Madurella mycetomi (brown‐black)
Exophilia jeanselmei
Acremonium spp. (white‐yellow)
—
—
Small ulcer with sinus tracts
Sulfur grains (white or black)
Tissue swelling
Lytic bone changes occur late; rare muscle invasion
Antifungal rarely effective; surgical excision
Systemic mycoses
Coccidiomycosis (San Joaquin Valley Fever)
Coccidioides immitis/C. posadasii
Large spherules,
Splendore–Hoepli phenomenon
Boxcars: barrel‐shaped arthroconidia alternating with empty cells
Southwestern US, Mexico, Central America
Primary pulmonary infection (60% asx)
Dissemination to CNS, bone
Skin lesions more verrucous. May develop EN or EM lesions
Itraconazole, fluconazole, amphoB
Paracoccidiomycosis (South American Blastomycosis)
Paracoccidioides brasiliensis
Mariner’s wheel (thin‐walled yeast with multiple buds)
Oval microconidia indistinguishable from Blastomyces
South America, Central America
Chronic granulomatous pulmonary disease
Disseminates to liver, spleen, adrenals, GI, nodes
Skin: granulomatous oral/ perioral lesions
*Men ≫̸ women: estrogen may inhibit growth
Ketoconazole
Blastomycosis (Gilchrist disease, North American Blastomycosis)
Blastomyces dermatitidis
Broad‐basedbbudding yeast with thick walls
Lollipop spores
Southeast US and Great Lakes
Primary pulmonary infection
Disseminates to CNS, liver, spleen, GU, long bones
Skin: verrucous lesion with “stadium edge” borders
Itraconazole, amphoB
Histoplasmosis (Darling disease)
Histoplasmosis capsulatum/
H. duboisii
Intracellular yeasts in macrophages (parasitized histiocytes, may see halo unlike Leish)
Tuberculate macroconidia
Mississippi/ Ohio river valley basin – bird/bat droppings
Most common: pulmonary infection (80–95%)
Dissemination to liver, BM, spleen, and CNS
Skin: molluscum‐like lesions in AIDS
Itrazconaozle, amphoB
Opportunistic mycoses
Candidiasis
Candida albicans
Pseudohyphae or true septate hyphae
Part of normal enteric flora
Infection is due to predisposing factors: impaired epithelial barrier: burns, maceration, wounds, occlusion, foreign bodies (dentures, catheters), and antibiotics
Constitutional disorders: DM2, polyendocrinopathy, and malnutrition
Immunodeficiency: cytotoxic agents, neutropenia, agranulocytosis, HIV, and chronic granulomatous disease
Topicals: nystatin, miconazole, clotrimazole
Systemic: SAF
Cryptococcosis
Cryptococcus neoformans
Encapsulated yeasts with surrounding clear halo, “tear drop budding”
Stain with mucicarmine, PAS, GMS, or India ink
Bird droppings – usually via pulmonary infection then hematogenous spread to lungs, bones, and viscera. Predilection for CNS.
Skin: nasopharygeal papules/pustules, subQ ulcerated abscess
AmphoB
fluconazole
Aspergillosis
Aspergillus flavus
A. fumigatus
A. niger
Phialides with chains of conidia (broom brush)
Septate hyphae 45° branching
Infection from inhalation of conidia → pulmonary aspergillosis
Allergic bronchopulmonary aspergillosis: hypersensitivity, no tissue invasion
Invasive/disseminated aspergillosis: angioinvasive
Allergic: steroid
Invasive: SAF
Zygomycosis/Mucormycosis
Hyphae broad ribbon like with 90° branching
Most commonly respiratory portal of entry → rhinocerebral infection
Associated with diabetic ketoacidosis
AmphoB, surgical excision
Rhizopus
Mucor
Absidia
Rhizoid opposite sporangia
No rhizoids
Rhizoids between sporangia
Penicilliosis
Penicillium marneffei
Histo‐like intracellular yeasts
Southeast Asia
Umbilicated lesions, 85% of affected patients have skin lesions
AmphoB, fluconazole
Viruses and diseases
Family
Examples
Replication site
Genome (+ sense; – antisense)
DNA
Poxviridae
Molluscipox: Molluscum
Orthopox: Vaccinia, smallpox, and cowpox
Parapox: Orf, milker’s nodule
Cytoplasm
dsDNA
Papillomaviridae
Human papilloma virus
Nucleus
dsDNA
Herpesviridae
HHV1: HSV1
HHV2: HSV2
HHV3: VZV
HHV4: EBV
HHV5: CMV
HHV6: Roseola infantum, reactivation increases drug‐induced hypersensitivity syndrome severity
HHV7: associated with Pityriasis rosea
HHV8: Kaposi sarcoma
Nucleus
dsDNA for all
Hepadnaviridae
HBV
Nucleus w/ RNA intermediate*
Gapped dsDNA
Adenoviridae
Human adenovirus
Nucleus
dsDNA
Parvoviridae
Erythema infectiosum
Nucleus
ssDNA
RNA
Paramyxoviridae
Measles, Mumps
Nucleus
− ssRNA
Togaviridae
Rubella, Chikungunya
Cytoplasm
+ssRNA
Rhabdoviridae
Rabies
Nucleus
− ssRNA
Retroviridae
HIV, HTLV
Nucleus
+ssRNA (dsDNA intermediate
Picornaviridae
Enterovirus (coxsackie; HAV)
Nucleus
+ssRNA
Flaviviridae
HCV, West Nile, Yellow fever, Dengue
Cytoplasm
+ssRNA
Filoviridae
Ebola, Marburg
cytoplasm
–ssRNA
Bunyaviridae
Hantavirus, Rift valley, Congo‐Crimean
cytoplasm
–ssRNA
Arenaviridae
Lassa
cytoplasm
–ssRNA
Human papilloma virus
Disease
Description
Associated HPV type
Verruca vulgaris
Common warts
1, 2, 4
Myrmecia
Large cup‐shaped palmoplantar warts
1
Verruca plantaris/palmaris
Plantar warts
1, 2, 27, 57
Butcher’s wart
Warty lesions from handling raw meat
2, 7
Verrucous carcinoma, foot
Epithelioma cuniculatum
2, 11, 16
Verruca planae
Flat warts
3, 10
Epidermodysplasia verruciformis
Inherited disorder of HPV infection and SCCs
3, 5, 8, 12, many others
Buschke and Löwenstein
Giant condyloma
6, 11
Condyloma acuminata
Genital warts
LOW RISK: 6, 11
HIGH RISK: 16, 18, 31
Flat condyloma: 42
Oral condyloma: 6, 11
Oral florid papillomatosis (Ackermann)
Oral/nasal, multiple lesions, smoking/irradiation/chronic inflammation
6, 11
Recurrent respiratory papillomatosis
Laryngeal papillomas
6, 11
Heck disease
(Focal epithelial hyperplasia)
Small white and pink papules in mouth
13, 32
Bowen’s disease
SCCIS
16, 18
Bowenoid papulosis
Red‐brown papules and plaques on the genital resembling genital warts. Histologically SCCIS/ high‐grade squamous intraepithelial lesion
16, 18
Erythroplasia of queyrat
Velvety erythematous plaque on the genital. Histologically SCCIS
16, 18
Stucco keratoses
White hyperkeratotic plaques on legs
23b, 9, 16
Ridged wart
Wart with preserved dermatoglyphics
60
Other viral diseases
Viral disease
Description
Cause
Boston exanthem
Roseola‐like morbilliform eruption on face and trunk, small oral ulcerations
Echovirus 16
Castleman disease (associated w/ POEMS and paraneoplastic pemphigus)
(Angio)lymphoid hamartoma: hyaline‐vascular type, plasma cell, and multicentric/ generalized types
HHV‐8
Dengue fever (virus may cause Dengue fever, Dengue hemorrhagic fever, or Dengue shock syndrome)
Rash in in 50% of patients, flushing erythema within 1–2 d of symptom onset, then 3–5 d later a generalized often asx maculopapular eruption with distinct white “islands of sparing,” 1/3 mucosal lesions, may be ecchymotic or petechial, incubation 3–14 d
Dengue flavivirus
Eruptive pseudoangiomatosis
Fever, transient hemangioma‐like lesions, usually children, often with halo
Echovirus 25 and 32
Erythema infectiosum (Fifth disease)
Children aged 4–10 yr, “slapped cheeks,” reticular exanthem, usually extremities, arthropathy in adults, anemia/hydrops in fetus, persistent in Sickle Cell
Parvovirus B19
Gianotti–Crosti syndrome (Papular acrodermatitis of childhood)
Children (often ≤4 yo) with acute onset of often asymptomatic, lichenoid papules on face and extremities, less on trunk
Various: HBV most common worldwide, EBV most common in the United States
Hand‐Foot‐and‐Mouth
Brief mild prodrome, fever, erosive stomatitis, acral and buttock vesicles, highly contagious, mouth hurts, skin asymptomatic
Various Coxsackie viruses, Coxsackie Virus A16, Enterovirus 71
Herpangina
Fever, painful oral vesicles/erosions, no exanthem
Coxsackie Groups A and B, various echoviruses
Hydroa vacciniforme
Vesiculopapules, photosensitivity, pediatric with resolution by early adulthood
EBV (when severe, EBV‐associated NK/T‐cell lymphoproliferative disorders)
Infectious mononucleosis (Glandular fever)
Two peaks: 1–6 yo and 14–20 yo; fever, pharyngitis, (cervical) lymphadenopathy, HSM, eyelid edema, 5% rash, leukocytosis, elevated LFTs; 90% get maculopapular exanthema with ampicillin/amoxicillin
EBV (also causes nasopharyngeal carcinoma, posttransplant lymphoproliferative disorder, African Burkitt lymphoma)
Kaposi sarcoma
Vascular tumors
HHV‐8
Kaposi varicelliform eruption (Eczema herpeticum)
Often generalized, crusted, vesiculopustular dermatitis; may be umbilicated*; fever, malaise, lymphadenopathy
HSV, may also occur with coxsackie, vaccinia, and other dermatitides
Lichen planus
Purple, Polygonal, Planar, Pruritic, Papules
HCV
Measles (Rubeola)
Prodrome – cough, coryza, conjunctivitis, Koplik spots. Then maculopapular rash spreads craniocaudally. Incubation 10–14 days
Paramyxovirus
Milker’s nodules
Similar to Orf
From infected cows
Paravaccinia/Parapoxvirus
Molluscum Contagiosum
Umbilicated papules in children and HIV, or as STD
Poxvirus; 4 MCV subtypes: MCV 1 is most common overall,
MCV 2 in immunocompromised
Monkeypox
Smallpox‐like but milder and lesions may appear in crops, with prominent lymphadenopathy, and without centrifugal spread
Monkeypox/Orthopoxvirus (smallpox vaccination is protective)
Oral hairy leukoplakia
Nonpainful, corrugated white plaque on lateral tongue in HIV or other immunosuppressed patients, + smoking correlation
EBV
Orf (Ecthyma Contagiousum)
Umbilicated nodule after animal contact, six stages; sheep, goats, reindeer; self‐limiting in ~5 weeks
Orf/Parapoxvirus
Papular/Purpuric stocking‐glove syndrome
Young adults, mild prodrome, enanthem, edema, erythema, petechiae, purpura, burning, pruritus on wrists/ankles
Various: Parvovirus B19, Coxsackie B6, HHV‐6
Pityriasis rosea
Usually asymptomatic papulosquamous exanthem
Possibly HHV‐7
Ramsey hunt
Vesicular lesions following geniculate ganglion on external ear, tympanic membrane, with ipsilateral facial paralysis and deafness, tinnitus, vertigo, oral lesions
VZV
Roseola infantum
(Exanthum subitum, Sixth disease)
Infants with high fever (×3 days) followed by morbilliform rash, 15% have seizure
HHV‐6B, rarely HHV‐6A or HHV‐7
Rubella (German measles)
Mild prodrome, tender LAN, pain with superolateral eye movements, morbilliform rash, spreads craniocaudally, petechial enanthem (Forschiemer spots), incubation 16–18 days
Togavirus
Smallpox
7–17 day incubation, 2–4 day prodrome (fever, HA, and malaise), then centrifugal vesiculopustular rash, lesions are all the same stage, respiratory spread
Variola/Orthopoxvirus
STAR complex
Sore throat, elevated Temperature, Arthritis, Rash
Various: HBV, Parvovirus B19, Rubella
Unilateral laterothoracic exanthem
Age <4 years, morbilliform or eczematous, often starts in axilla, unilateral then spreads
Various: EBV, HBV, Echovirus 6
Infections/Bugs
Vector‐borne diseases
Disease
Cause
Vector/transmission
Treatment
Acrodermatitis chronica atrophicans
(Pick‐Herxheimer disease)
Borrelia afzelii,
Borrelia garinii
Ixodes ricinus, Ixodes hexagonus,
Ixodes persulcatus
Amoxcillin, doxycycline, cefotaxime, penicllin G
African tick‐bite fever
Rickettsia africae
Amblyomma hebraeum,
Amblyomma variegatum
Doxycycline
African trypanosomiasis (sleeping sickness)
–Winterbottom sign (posterior cervical LAN)
–Kerandel’s sign (hyperesthesia)
Trypanosoma brucei gambiense (West Africa)
Tsetse fly (Glossina morsitans)
Pentamidine isethionate (hemolytic stage)
Melarsoprol or eflornithine (CNS involvement)
Trypanosoma brucei rhodesiense (East Africa)
Tsetse fly (Glossina morsitans)
Suramin (hemolytic stage)
Melarsoprol (CNS involvement)
Bacillary angiomatosis
Bartonella henselae, Bartonella quintana
Cat flea (Pediculus humanus)
Erythromycin, doxycycline
Brazilian spotted fever
Rickettsia ricketsii
Ixodid tick Amblyomma cajennense
RESERVOIR: Capybara
Doxycycline
Carrion disease
(Bartonellosis, Oroya fever, Verruga peruana)
Bartonella bacilliformis
Sandfly (Lutzomyia verrucarum)
Chloramphenicol (due to frequent superinfxn with salmonella)
Cercarial dermatitis (Swimmer’s itch)
Cercariae of animal schistosomes
Snail
Topical corticosteroids
Chagas disease (American trypanosomiasis)
Trypanosoma cruzi
Reduviid bug (assassin bug, kissing bug)
Benznidazole, nifurtimox
Cutaneous larva migrans (Creeping eruption)
Ancylostoma braziliense, Ancylostoma caninum
Animal feces
Albendazole, ivermectin OR
Thiabendazole topically
Cysticercosis
Taenia solium
Contaminated pork
Albendazole, praziquantel
Dengue fever
Flavivirus
Aedes aegypti or albopticus
Supportive Tx
Dracunculiasis
Dracunculus medinensis (Guinea fire worm)
Cyclops water flea ingestion
Slow extraction of worm + wound care
Oral metronidazole facilitates removal
Ehrlichiosis, human monocytic (HME)
Ehrlichia chaffeensis
Amblyomma americanum
Doxycycline, rifampin (pregnancy)
Ehrlichiosis, human granulocytic (HGE), and human granulocytic anaplasmosis (HGA)
Ehrlichia ewingii (HGE),
Anaplasma phagocytophilum (HGA)
Ixodes persulcatus and Dermacentor variabilis
Doxycycilne, rifampin (pregnancy)
Elephantiasis tropica (Lymphatic filariasis)
Wuchereria bancrofti,
Brugia malayi, Brugia timori
Culex, Aedes, and Anopheles mosquitos
Diethylcarbamazine
Erysipeloid (of Rosenbach)
Erysipelothrix rhusiopathiae
Fish, shellfish, poultry, and meat
Penicillin G, Cipro, erythromycin/rifampin
Glanders (Farcy)
Burkholderia (Pseudomonas) mallei
Horses, mules, and donkeys
Augmentin, doxycycline, TMP‐SMX
Kala‐azar
(Visceral leishmaniasis)
L. donovani, L. infantum (Old World)
L. chagasi (New World)
Phlebotomus sand fly
Lutzomyia sand fly
Pentavalent antimony (sodium stibogluconate) or amphotericin
Leishmaniasis, New World (Muco) Cutaneous (Chiclero Ulcer, Uta, Espundia, Bay Sore)
L. mexicana, L. braziliensis
Lutzomyia sand fly
Pentavalent antimony (sodium stibogluconate) or amphotericin
Leishmaniasis, Old World Cutaneous (Oriental/Baghdad/Dehli Sore)
L. tropica; L. major; L. aethiopia, L. infantum
Phlebotomus sand fly
RESERVOIR: Rodents
Pentavalent antimony (sodium stibogluconate)
Loiasis (Calabar, Fugitive swelling)
Loa loa
Tabanid (horse/mango) fly,
Chrysops (red, deer) fly
Diethylcarbamazine
Lyme disease
US: Borrelia burgdorferi
EUROPE: B. garinii and B. afzelli
NE/GREAT LAKES: Ixodes scapularis/dammini
WEST US: I. pacificus
EUROPE: I. ricinus
Doxycycline
Amoxicillin if pregnancy or <9 yo
Mediterranean spotted fever
(Boutonneuse fever)
Rickettsia conorii
Rhipicephalus sanguinous (dog tick)
Doxycycline, chloramphenicol, and floroquinolone
Melioidosis (Whitmore disease)
Burkholderia (Pseudomonas) pseudomallei
Tropical soil, water
IV ceftazidime (high‐intensity phase) then TMZ‐SMX and Doxycycline
Myiasis
Dermatobia hominis (botfly),
Cordylobia anthropophaga (tumbu fly), Phaenicia sericata (green blowfly)
Mosquito (for Dermatobia hominis)
Removal of larvae and treatment with abx for superinfection
Onchocerciasis (River blindness)
Onchocerca volvulus
Simulium species (black fly)
Ivermectin
Plague (Bubonic)
Yersinia pestis
Xenopsylla cheopis (rat flea)
Streptomycin, gentamicin
Q Fever
Coxiella burnetii
Dried tick feces inhalation
Doxycycline
Rat‐bite fever (Haverhill, Sodoku)
Spirillium minus (Asia/Africa),
Streptobacillus moniliformis (US)
Rat bite, scratch, excrement, contaminated food
Penicillin
Relapsing fever – Louse‐borne
Borrelia recurrentis (Africa, South America)
Pediculosis humanus,
Doxycycline
Relapsing fever – Tick‐borne
Borrelia duttonii, Borrelia hermsii (Western US)
Ornithodorus genus (soft bodied ticks)
Doxycycline
Rickettsialpox
Rickettsia akari
Allodermanyssus (Liponyssoides) Sanguineus (house mouse mite)
RESERVOIR: Mus musculus – domestic mouse
Doxycycline
Rift valley fever
Phlebovirus, bunyavirus
Aedes
Supportive Tx, ribavirin (investigational)
Rocky mountain spotted fever
Rickettsia rickettsii
Dermacentor andersoni, Dermacentor variabilis
Doxycycline
Schistosomiasis/Bilharziasis
(Cercarial dermatitis, Katayama fever, late allergic dermatitis, perigenital granulomata, extragenital infiltrative)
Schistosoma mansoni (GI),
S. japonicum (GI),
S. haematobium (urinary system)
Snail
Praziquantel
Scrub typhus (Tsutsugamushi fever)
Rickettsia/Orientia tsutsugamushi
Larval stage of trombiculid mite (chigger, Trombicula/Leptotrombidium akamushi)
Doxycycline
South African tick‐bite fever
Rickettsia conorii
Rhipicephalus simus, Haemaphysalis leachii, Rhipicephalus mushamae
Doxycycline
Sparganosis
Spirometra (dog and cat tapeworm larvae)
Application/ingestion of infected frog, snake, or fish
Surgical removal
Toxoplasmosis
Toxoplasma gondii
Cat feces, undercooked meat, milk
Pyrimethamine and sulfadiazine
First trimester: spiramycin
Trench (Quintana) fever
Bartonella quintana
Pediculus humanus corporis
Doxycycline, erythromycin
Trichinosis
Trichinella spiralis
Undercooked pig, wild game
Steroids for severe symptoms and
mebendazole or albenazole
Tularemia (Deer fly fever, Ohara disease)
Francisella tularensis
Rabbit, Dermacentor andersonii,
Amblyomma americanum,
Chrysops discalis (deer fly), domestic cats
Streptomycin
Typhus, endemic; Murine/Flea‐borne typhus
Rickettsia typhi
Xenopsylla cheopis (rat flea)
Doxycycline
Typhus, epidemic; Brill‐Zinsser disease/relapsing Louse‐Borne typhus)
Rickettsia prowazekii
Pediculus humanus, squirrel fleas
RESERVOIR: Glaucomys volans‐flying squirrel
Doxycycline
Weil disease (leptospirosis)
Leptospira interrogans icterohaemorrhagiae
Rat urine
Doxycycline, penicillin, ampicillin, and Amoxicillin
West Nile fever
Arbovirus
Aedes, culex, and anopheles
Supportive Tx
Yellow fever
Arbovirus
Aedes aegypti
Supportive Tx
Creatures in dermatology
Creature
Scientific name
Special features
Spiders
Brown recluse spider
Loxosceles reclusa
Black widow spider
Latrodectus mactans
Jumping spider
Phidippus formosus
Wolf spider
Lycosidae
Sac spider
Chiracanthium
Hobo spider
Tegenaria agrestis
Green lynx spider
Peucetia viridans
Tarantula
Theraphosidae
Caterpillers Lepidoptera (urticaria after contact with hairs)
Puss/Asp
Megalopyge opercularis
Iomoth
Automeris io
Gypsy/Tent moth
Lymantria dispar
Saddleback
Sibine stimulea
Hylesia moth
Hylesia metabus
Lonomia caterpillar
Lonomia achelous/obliqua
Flies
Black fly
Simulium
Sand fly
Phlebotomus
Lutzomyia
Tsetse fly
Glossina
Deer fly
Chrysops
Botfly larvae
Dermatobia hominis, Callitroga americana (US)
Mosquitoes Culicidae
Anopheles
Aedes
Culex
Fleas Siphonaptera
Human flea
Pulex irritans
Cat flea
Ctenocephalides felis
Rat flea
Xenopsylla cheopis
Sand/Chigoe flea
Tunga penetrans
Beetles
Rove beetle
Paederus eximius
Blister beetle
Lytta vesicatoria/Spanish fly
Carpet beetle
Attagenus megatoma and A. scrophulariae
Lice
Pubic (Crab)
Pthirus pubis
Head lice
Pediculus capitis
Body lice
Pediculus humanus corporis
Rickettsia prowazekii → epidemic typhus
Mites
Scabies
Sarcoptes scabiei hominis
Straw itch mite
Pyemotes tritici
Demodex
Demodicidae
Grain mite
Acarus siro
Cheese mite
Glyciphagus
Grocery mite
Tyrophagus
Harvest mite (Chigger)
Trombicula alfreddugesi
Dust mite
Dermatophagoides
Euroglyphus
House mouse mite
Allodermanyssus sanguineus
Walking dander
Cheyletiella
Fowl mite
Ornithonyssus,
Dermanyssus
Copra Itch
Tyrophagus putrescentiae
Others
Scorpions
Centruroides sculturatus and C. gertschi
Bedbugs
Cimex Lectularius
Bees, wasps, hornets, ants
Hymenoptera
Fire ant
Solenopsis
Reduviid bug
Hemiptera
Centipedes
Chilopoda
Millipedes
Deplopoda
Water Creatures
Leeches
Sea urchin
Sea cucumber
Dolphins
Schistosomes (Flukes)
– nonhuman host
Schistosomes (Flukes)
– human host
Stronglyoides stercoralis (Threadworm)
Ancylostoma caninum,
A. braziliense (Hookworm)
Cnidarian ‐ Jellyfish, Portuguese man of war, sea anemone, coral, and hydroids. Stingers (nematocytes) break through skin causing pain and potential systemic symptoms. Use 3–10% acetic acid or vinegar to fix nematocytes to prevent firing and toxin release
Box jellyfish
Portuguese Man of War
Sea anemone (Edwardsiella lineate)
Thimble jellyfish (Linuche unguiculata)
Exotic pets, others
Iguana
Hedgehog
Cockatoo, Pigeon
Chincilla
Fish/Fish tank/Swimming pool
Flying squirrel
Lambs (lambing)
CONTACT AND PLANT DERMATITIS
Patch testing
−
Negative – no reaction
?
Doubtful reaction: Macular erythema only
+
Weak reaction: Nonvesicular – erythema, infiltration, and possibly papules
++
Strong reaction: Edematous or vesicular, erythema and papules
+++
Extreme reaction: Spreading, bullous, and ulcerative
IR
Irritant reaction
NT
Not tested
T.R.U.E Test (Thin‐layer Rapid Use Epicutaneous Test): 36 chambers
Panel 1.3
Panel 2.3
Panel 3.3
1
Nickel sulfate
13
p‐tert‐Butylphenol formaldehyde resin (PTBP)
25
Diazolidinyl urea
2
Wood alcohols
14
Epoxy resin
26
Quinoline mix
3
Neomycin sulfate
15
Carba mix
27
Tixocortal‐21‐pivalate
4
Potassium dichromate
16
Black rubber mix
28
Gold sodium thiosulfate
5
Caine mix
17
Cl Me Isothizolinone
29
Imidazolidinyl urea
6
Fragrance mix
18
Quarterium 15
30
Budesonide
7
Colophony
19
Methydibromo‐glutaronitrile
31
Hydrocortison‐17‐butyrate
8
Paraben mix
20
p‐Phenylenediamine
32
Mercaptobenzothiazole
9
Negative control
21
Formaldehyde
33
Bacitracin
10
Balsamof Peru
22
Mercapto mix
34
Parthenolide
11
Eithylenediamine dihydrocholoride
23
Thimerasal
35
Disperse Blue 106
12
Colbalt dichloride
24
Thiuram mix
36
2‐Bromo‐2‐nitro‐propane‐1‐3‐diol (bronopol)
Common contact allergens
Allergen (standard testing concentration)
Uses/products/cross‐reactions (X‐RXN)
T.R.U.E test
NACDG rank*
Metal
Nickel
(2.5% pet.)
– Jewelry, watches, alloys, coins, buttons and belt buckles, eyelash curlers, kitchen utensils, scissors, razors, canned food, and electronics (phones)
– Dietary nickel: legumes, dark leafy green vegetables, chocolate, and oat
Can have coexisting allergies to chromate and cobalt
*Dimethylglyoxime – to detect nickel (turns pink)
#1
1
Cobalt
(1.0% pet.)
Mixed with metals for strength
– Cement, cosmetics, vitamin B12 injections, pigment in porcelain, paint, crayon, glass, pottery, and blue tattoos
X‐RXN: nickel, chromate
#12
14
Potassium dichromate/chromium
(0.25% pet.)
– Tanned leather, cement, mortar, matches, anti‐rust products, paint, plaster, GREEN dyes/ tattoos (pool/card table felt), metal working, chromic surgical gut suture, and implants
X‐RXN: nickel, cobalt
#4
40
Gold sodium thiosulfate
(0.5% pet.)
– Jewelry, dental restorations, electronics, and glass frames
X‐RXN: nickel, cobalt
#28
—
Resin/plastics/glue
2‐Hydroxyethyl methacrylate/HEMA
(2% pet.)
– Artificial nails, dental work
—
30
Epoxy resin/Bisphenol A
(1% pet.)
Allergens: bisphenol A, epichlorohydrin
USES: Resin for adhesive
– Glues, plastics, adhesives, PVC products, electrical insulation, paints, and protective coatings
#14
35
Methyl methacrylate
(2% pet.)
– Artificial nails, dental work, glue for surgical prostheses, and exterior latex house paint
—
46
Ethyl acrylate
(0.1% pet.)
Resin, plastics, rubber, and denture
—
51
p‐tert‐Butylphenol formaldehyde resin (PTBP)
USES: adhesive
– Glues, shoes/watchband/handbag (glued leather products), plywood, disinfectants, rubber, varnish, printer inks, and fiberglass
may cause depigmentation
X‐RXN: formaldehyde
#13
62
Ethyl cyanoacrylate
(10% pet.)
“Superglue”
– Artificial nails glue, liquid bandage
—
66
Toulene‐sulfonamide/tosylamide formaldehyde resin
(10% pet.)
Nail lacquer/hardener: eyelid, face, neck, and finger dermatitis
—
47
Rubber compound
Carba mix
(3% pet.)
USES: Rubber stabilizer, fungicides, and pesticides
– Elastic bands, condoms, shoes, cements, erasers, health‐care equipments (gloves, masks, and tubing)
X‐RXN: thiurams
#15
11
Thiuram mix
(1% pet.)
USES: Rubber additives, prevents degradation of rubber products
– Gloves, adhesive, latex, condoms, neoprene, fungi and pesticides, and Disulfiram
X‐RXN: carba mix, rubber additives
#24
18
Black rubber mix
(0.6%pet.)
Isopropyl PPD, cyclohexyl PPD, and diphenyl PPD
USES: Rubber stabilizer
– Black and gray rubber products: tires, rubber boots, eyelash curlers, scuba suits, and balls
X‐RXN: disperse dyes, hydrochlorothiazide, ester anesthetic (PABA), and sulfonamides
#16
45
Mercapto mix
(1% pet.)
USES: Rubber accelerator
– Rubber products: gloves, makeup sponges, undergarments, and tires
#22
61
Mercapto‐benzothiazole/MBT
(1% pet.)
USES: Rubber accelerator
– Rubber shoes, tires, undergarments, shoes, and neoprene
Co‐sensitizer: rubber additives such as dibutyl and diphenyl thiourea
#32
58
Mixed dialkyl thioureas
(1% pet.)
Rubber antioxidant
– Wet suits, shoe insoles, adhesives, copy paper, and photography
—
48
Vehicle and cosmetic ingredients
Lanolin/
Wool alcohol
(50% pet.)
USES: Emulsifier
From: sheep sebum (amerchol, cholesterol, lanosterol, agnosterol, and alcohol)
– Cosmetics, soaps, adhesives, and topical agents
X‐RXN: Aquaphor, Eucerin (cetyl or stearyl alcohols)
#2
9
Propylene glycol
(30% aq.)
Dimer alcohol to increase drug solubility
– Vehicle base in topical meds, valium, lubricant jelly; brake fluid, and antifreeze
—
15
Cocamidopropyl Betaine
(1% aq.)
Nonionic surfactant from coconut oil
Antigens: amidoamine, DMAPA, and CAPB
– Shampoo (“no more tears”), liquid soaps
Usually facial pattern rash
—
24
Cocamide DEA
(0.5% pet.)
Shampoos, soaps
—
37
Cocamidopropyl betaine
(1% aq.)
Nonionic surfactant from coconut oil
Antigens: amidoamine, DMAPA, and CAPB
– Shampoo (“no more tears”), liquid soaps
Usually facial pattern rash
—
24
Benzyl alcohol
(10% pet.)
Solvent, preservative, and anesthetic
– Plants, essential oils, foods, cosmetics, medications, and paints/lacquers
—
57
Ethylenediamine dihydrochloride
(1% pet.)
Industrial stabilizer
– Topical antibiotic/steroid creams (Mycolog cream); dye, rubber, resin, waxes, fuel additive, corrosion inhibitors, and plastic lubricants
X‐RXN: DETA, epoxy amines, hydroxyzine, aminophylline, and phenothiazine
#11
59
Medicaments
Bacitracin
(20% pet.)
– Triple antibiotics
Risk groups: leg ulcers, post‐op, chronic otitis externa
Co‐sensitivity: neomycin
#33
10
Neomycin sulfate
(20% pet.)
Aminoglycoside group
– Triple antibiotics, ear/eye drops
X‐RXN: aminoglycosides
Co‐sensitivity: bacitracin
#3
17
Chloroxylenol
(1% pet.)
– Carbolated vaseline, personal‐care products, EKG paste, and surgical scrubs
—
56
Lidocaine
(15% pet.)
Amide anesthetic
Usually allergy due to paraben preservative and not amide
—
49
Benzocaine
(5% pet.)
PABA derivative, ester anesthetic
X‐RXN: procaine, cocaine, PABA, sulfa meds, thiazide, and PPD
#5: Caine mix
54
Dibucaine
(2.5% pet.)
Amide anesthetic
X‐RXN: lidocaine, bupivicaine
#5: Caine mix
63
Tetracaine
(2% pet.)
PABA derivative, ester anesthetic
X‐RXN: procaine, cocaine, PABA, sulfa meds, thiazide, and PPD
#5: Caine mix
—
Corticosteroids
Four groups based on structure:
A – HC/Prednisone – most allergenic
B – TMC acetonide (also budesonide, desonide)
C – Betamethasone, dexamethasone
D1 – Clobetasone‐17‐propionate
D2 – Hydrocortisone‐17‐butyrate
—
—
Tixocortol pivalate (1% pet.)
Test for group A corticosteroids
(Hydrocortisone and Prednisone)
– Medicaments, nasal spray
#27
19
Budesonide
(0.1% pet.)
Test for group B corticosteroids (TMC and budesonide)
X‐RXN: D2 steroids (hydrocortisone‐17‐butyrate)
#30
42
Desoximetasone
(1% pet.)
Test for group C corticosteroids (Betamethasone)
X‐RXN: none – more hypoallergenic
—
69
Clobetasol‐17‐propionate
(1% pet.)
Test for group D1 corticosteroids
—
65
Hydrocortisone‐17‐butyrate
(1% pet.)
Test for group D2 corticosteroids
X‐RXN: group A steroids (hydrocortisone)
#31
68
Fragrances
Fragrance mix I – 8 fragrances
(8.0% pet.)
1. α‐Amyl cinnamic aldehyde
2. Cinnamic alcohol
3. Cinnamic aldehyde (toothpaste, gum, and lipstick)
4. Hydroxycitronellal – synthetic, floral
5. Isoeugenol
6. Eugenol – clove
7. Evernia prunastri – oak moss/lichen extract
8. Geraniol – geranium
Found in personal hygiene products (perfumes, flavoring agents, and soaps), household cleaners, air fresheners, paper products, foods and flavorings, and candles
X‐RXN: colophony, wood tars, turpentine, propolis, benzoin, storax, and balsam of Peru
#6
2
Balsam of Peru – Myroxylon pereirae resin
(25% pet.)
Cinnamic acid, cinnamyl cinnamate, benzyl benzoate, benzoic acid, vanillin, and eugenol
– Fragrances, spices (cloves, cinnamon, and Jamaican pepper), flavoring agent (wine, tobacco, vermouth, and cola), mild antimicrobial properties, and candles
X‐RXN: Colophony, benzoin, propolis, and fragrance mix
#10
3
Fragrance mix II (14% pet.)
1. Citronellol
2. Hexyl cinnamal
3. Citral
4. Coumarin
5. Farnesol
6. Hydroxyisohexyl 3‐cyclohexene
carboxaldehyde (Lyral)
Found in personal hygiene products
—
8
Cinnamic aldehyde (1.0% pet.)
Oral hygiene products (toothpaste)
Allergen is component of Frag mix I and balsam of Peru
—
13
Colophony – rosin, abietic acid
– Adhesives, cosmetics, epilation wax, polish, paint, chewing gum, instrument rosin (violin), topical salves, paper products, wood products (sawdust, wood fillers); from conifer
X‐RXN: wood tars, fragranes, spices, and rosin esters
#7
29
Limonene
(2% pet.)
– Citrus peels, fragrance additive, sanitizers, cleansers, and degreasers
—
70
Preservatives – formaldehyde releasing
Quaternium‐15
(2% pet.)
Sensitivity may be to formaldehyde
#1 cause of hand dermatitis
– topical medications, soaps, shampoos, moisturizers, industrial polishes, waxes, ink, latex paints, and adhesives
#18
5
Formaldehyde
(1% aq.)
– Ubiquitous – fabric finishes (waterproof, anti‐wrinkle), cosmetics, cleansers, paper products, paint, pressed wood construction material, and embalming fluids
X‐RXN: Formaldehyde‐releasing preservatives: quaternium‐15, imidazolidinyl urea, diazolidinyl urea, and DMDM‐hydantoin
#21
7
Diazolidinyl urea (1% pet.)
Germall II
– cosmetics, personal‐care products
X‐RXN: Formaldehyde‐releasing preservatives
—
20
DMDM hydantoin (1% pet)
—
23
Bronopol/2‐Bromo‐
2‐nitropropane‐1,3‐diol
(0.5% pet.)
– Topical medications, cosmetics, and personal‐care products
X‐RXN: Formaldehyde‐releasing preservatives
#36
26
Imidazolidinyl urea/Germall 115/Tristat
(2% pet.)
– Topical medications, cosmetics, skin/hair products, adhesive, and latex emulsions
X‐RXN: Formaldehyde‐releasing preservatives
#25
28
Preservatives – non‐formaldehyde releasing
MCI/MI (Methyl‐choloro‐isothiazinolone)/Kathon CG
(0.01% aq.)
USES: biocide and preservative
– Personal‐care products, cosmetics, hair/skin products (Eucerin), household products (toilet paper, baby wipes), permanent waves, and latex emulsions
#17
4
Iodopropyl butyl carbamate
(0.1% pet.)
– Personal‐care products, baby wipes, and cosmetics
—
12
Methyldibromo glutaronitrile/MDBGN/Euxyl K400
(1.0 % pet.)
USES: Preservative to prevent chemical change or microbial action
– Cosmetic/personal‐care products, paper towels, cutting oils, and adhesives
#19
16
Paraben mix
(12% pet.)
Methyl, Ethyl, Propyl, Butyl, Benzyl p‐hydroxybenzoate
USES: preservatives in personal‐care products, cosmetics, and medication
X‐RXN: PABA, PPD
*paraben paradox – may only react on involved skin, patch test to normal skin is negative
#8
22
Thimerosal
(0.1% pet.)
Components: thiosalicylic acid and ethyl mercuric chloride
– Preservative/antiseptic/vaccine/eye drops
X‐RXN: piroxicam, mercury
*Frequently allergen is not relevant
#23
—
Quinoline mix
Components: Clioquinol and Chlorquinaldol
– Preservative in antifungals, antibacterial medications, and paste bandage
X‐RXN: vioform, diiodoquin, and quinoloar
#26
—
Hair care
PPD/p‐Paraphenylenediamine
(1% pet.)
Blue‐black aniline dye
– Permanent hair dyes, henna tattoos, photography solutions, printer inks, oils, gasoline, and black rubber products
X‐RXN: pro/benzocaine, PABA, azo‐ and aniline dyes, sulfas, and para‐aminosalicylic acid
#20
6
Ammonium persulfate
(2.5% pet.)
Bleaching agent
– Hair bleach, flour
Contact urticaria, anaphylactoid rxn
—
—
Glyceryl thioglycolate/GTG
(1% pet.)
Acidic perming/permanent wave solutions
Chemical remains in hair shaft for months
—
—
Others
Disperse Blue 106
(1% pet.)
Fabrics colored dark blue, brown, black, purple, and green
X‐RXN: Disperse blue 124, para‐phenylenediamine
#35
43
Latex
Sap from the rubber tree Hevae brasiliensis
– Gloves, condom, and balloon
High risk: children with spina bifida, health‐care workers
X‐RXN: avocado, banana, chestnut, kiwi, and papaya
RAST test, prick test
—
Gluteraldehyde
(1% pet.)
Cold sterilizing solution
Health‐care workers, embalming fluid, electron microscopy, and hand cleansers
X‐RXN: formaldehyde
—
53
Propolis
(10% pet.)
Dimethylallyl ester of caffeic acid
– Bee glue, lipstick, ointments, and mascara
– Organic cosmetics
—
32
Parthenolide
(3 mcg/cm2)
Plants: daisies, feverfew, and magnolia
– Natural remedies
#34
—
Allergic vs. irritant contact dermatitis
Allergic contact
Irritant contact
Frequency
Less common (20%)
More common (80%)
Reaction
Immunologicl/Type IV delayed‐type hypersensitivity (Th1)
Non‐immunologic/Local toxic effect
Symptoms
Itchy, common on the hands, face, and neck
More painful and burning (rather than itchy)
Presentation
Hands, face, and neck
Erythema, edema, vesicles, papules, and lichenification
Erythema, edema, desquamation, and fissures
Onset
Hours to days
Usually minutes to hour
Distribution
May be focal or spread beyond area of exposure, appear in ectopic
Lesions restricted to areas where irritant damages the skin
Sensitization
Required. Usually takes 10–14 days. Upon reexposure, rash appears in 12–48 hours.
No sensitization. Can occur from single application without prior exposure or with multiple repeated applications. Affects everyone
Risk if atopic
Decreased
Increased
Cross‐reaction
Can occur
No cross‐reaction
Antigen
Requires lipophilic, low‐molecular weight haptens
N/A
Allergen‐specific lymphocytes not involved
Concentration
Independent – can be low dose
Dependent (dose response)
Diagnosis
Patch testing
History and physical
Negative patch test
Allergens – location specific
Location
Tips
Allergens
Hands/arms
Common to be combination of ICD and ACD
25–40% Irritant
25–75% ACD
Periorbital/eyelids
Most common – cosmetics
Lip (cheilitis)/perioral
Should get eval for ACD
85% in females
Scalp and neck
Frequently personal‐use products
Axillary
Usually deodorants, textile
Or systemic contact derm when feet and groin are also involved
Antiperspirant rarely cause ACD
Anogenital
Topically applied products
44% ACD
21% Irritant to soap and cleansers
Feet
Consider patch test in patients with unexplained chronic dermatitis in lower extremities, feet, and/or sole
Feet: Rubber chemicals, adhesives, leather in shoes
Legs
Consider patch test in patients with unexplained chronic dermatitis in lower extremities, feet, and/or sole
Legs: topically applied products
Features suggestive of specific irritant/toxin
Acne/folliculitis
Arsenic, oils, glass fibers, asphalt, tar, chlorinated naphthalenes, and polyhalogenated biphenyls
Miliaria
Occlusion, aluminum chloride, UV, and infrared
Alopecia
Borax, chloroprene dimers
Granulomatous
Silica, beryllium, keratin, talc, and cotton
Plants and Dermatoses
Plants causing non‐immunologic contact urticaria
Plants causing mechanical irritant dermatitis
Plants causing chemical irritant dermatitis
Chemical
Plant
Scientific name
Calcium oxalate
Daffodil
Narcissus spp. (Amaryllidaceae)
Century plant
Agave americana (Agavaceae)
Dumb cane
Philodendrom
Dieffenbachia picta and Philodendron spp. (Araceae)
Pineapple
Ananas cosmosus (Bromeliaceae)
Hyacinth
Hyacinthus orientalis (Liliaceae)
Rubarb
Rheum rhaponticum (Polygonaceae)
Thiocyanates
Garlic
Allium sativum (Alliaceae)
Black mustard
Brassica nigra (Brassicaceae)
Radish
Raphanus sativus (Brassicaceae)
Cashew nut shell oil
Cashew tree
Anacardium occidentale (Anacardiaceae)
Bromelin
Pinapple
Ananas cosmosus (Bromeliaceae)
Phorbol esters, diterpenes (latex)
Poinsetta
Euphorbia pulcherrina (Euphorbiaceae)
Protoanemonin
Buttercup
Ranunculus spp. (Renunculaceae)
Capsaicin
Chili pepper
Capsicum anuum (Salanaceae)
Phytophotodermatoses
Plant allergic contact dermatitis
Allergen
Family
Plant (Scientific name)
Urushiol
Anacardiaceae
Poison ivy/oak/sumac (Toxicodendron vernix)
Cashew nut tree (Anacardium occidentale)
Mango (Mangifera indica)
Cross‐reactions: Ginko biloba, Grevillea
Brazilian pepper tree (Schinus terebinthifolius, Florida Holly)
Indian marking tree nut (Semecarpus anacardium)
Japanese lacquer tree (Toxicodendron verniciflua)
Rengas tree (Gluta spp.)
Sesquiterpene lactones
Poisonwood tree (Metopium toxiferum)
Asteraceae (Compositae)
Feverfew (Tanacetum parthenium)
Chrysanthemum (X Dendranthema)
Dandelion (Taraxacum officinale)
Sunflower (Helianthus annuus)
Scourge of India (Parthenium hysterophorus, wild feverfew)
Daisy (Leucanthemum spp.)
Ragweed (Ambrosia spp.)
Marigold (Tagetes spp.)
Artichoke (Cynara scolymus)
Lettuce (Lactuca sativa)
Endive (Cichorium endiva)
Chicory (Cichorium intybus)
Chamomile, mugwort (Artemisia spp.)
Yarrow (Achillea millefolium)
Diallyl disulfide
Alliaceae
Onion (A. cepa)
Garlic (A. sativum)
Leek (A. porrum)
Chive
Tuliposide A
Alstromeriaceae and Lillaceae
Tulip, Peruvian lily (A. auriantiaca and A. ligtu)
Primin
Primulaceae
Primrose (Primula obconica)
Lamiaceae
Peppermint (menthol), spearmint (carvone), lavender, thyme
D‐limonene
Myrtaceae
Tea tree (Melaleuca spp.)
Colophony and turpentine/carene
Pinaceae
Pine tree (Pinus spp.)
Spruce tree (Picea spp.)
Ricin
Castor bean
Ricinus communis
Abrin
Jequirity bean
Abrus precatorius
Usnic acid, evenic acid, atronorin
Lichens
TUMORS AND INFILTRATES
Cutaneous T Cell Lyphoma
CTCL WHO‐EORTC Classification – Relative Frequency and 5‐year Survival
Relative Frequency (%)
5‐Year Survival (%)
Indolent cutaneous T‐cell and NK‐cell lymphoma
Mycosis fungoides
44
88
Follicular MF
4
80
Pagetoid reticulosis
<1
100
Granulomatous slack skin
<1
100
Cutaneous anaplastic CD30+ large cell lymphoma
8
95
Lymphomatoid papulosis
12
100
Subcutaneous panniculitis‐like T‐cell lymphoma
1
82
CD4+ small/medium pleomorphic T‐cell lymphoma
2
75
Aggressive cutaneous T‐cell and NK‐cell lymphoma
Sézary syndrome
3
24
Cutaneous aggressive CD8+ T‐cell lymphoma
<1
18
Cutaneous γ/δ T‐cell lymphoma
<1
—
Cutaneous peripheral T‐cell lymphoma unspecified
2
16
Cutaneous NK/T‐cell lymphoma, nasal‐type
<1
—
Mycosis Fungoides Variants
Clonality studies
CTCL Workup
CTCL (TNMB) staging
T (Skin)
N (Nodes)
M (Viscera)
B (Blood)
T1 = Patch/plaque < 10%
T1a = patch only
T1b = plaque ± patch
T2 = Patch/plaque > 10%
T3 = Tumor(s)
T4 = Erythroderma >90%
N0 = None
N1 = Palpable nodes, path (−)
N2 = Palpable nodes, path (+), nodal architecture unaffected
N3 = Palpable nodes, path (+), nodal architecture effaced
Nx = Palpable nodes, no histologic confirmation
M0 = None
M1 = Visceral
involvement
B0 = <5% Sezary cells
B1 = >5% Sezary cells, low blood tumor burden
B2 = high blood burden (1000/ml Sezary cells and positive clone)
Stage
Clinical involvement
Clinically enlarged nodes
Histologically + nodes
TNMB
5‐year survival (%)*
IA
IB
Patch/plaque < 10%
Patch/plaque > 10%
T1 N0 M0
T2 N0 M0
96
73
IIA
IIB
Patch/plaque
Tumor(s)
+Nodes
±Nodes
−Path
−Path
T1–2 N1 M0
T3 N0‐1 M0
73
44
IIIA
IIIB
Erythroderma
Erythroderma
−Nodes
+Nodes
−Path
−Path
T4 N0 M0
T4 N1 M0
44
IVA
IVB
Any skin
Visceral involvement
+Nodes
+ Path
T1–4 N2–3 M0
T1–4 N0–3 M1
27
CTCL Treatment Algorithm
Stage
First line
Second line
Experimental
IA
SDT or no therapy
IB, IIA
SDT
PUVA, NB/BB UVB
TSEB
Radiotherapy
IFN‐α
PUVA + IFN‐α, Retinoids, or Baxarotene
Low‐dose MTX
HDAC‐inhibitors (vorinostat, romidepsin)
Cytokines (i.e. Il‐2, IL‐12, and IFN‐γ)
Pegylated liposomal doxorubicin
Chlorodeoxyadenosine
IIB
TSEB + Superficial radiotherapy
Combination (2 of 3) tx w/ IFN‐α, PUVA, or Retinoids
HDAC‐inhibitors (vorinostat, romidepsin)
Denileukin Diftitox
Baxarotene
IFN‐α
Chemotherapy
Brentuximab vedotin
Autologous PBSCT, mini‐allograft
Zanolimumab
III
PUVA ± IFN‐α or Retinoids
ECP ± IFN‐α
MTX
IFN‐α
HDAC‐inhibitors (vorinostat, romidepsin)
TSEB
Denileukin diftitox
Bexarotene
Chemotherapy
Alemtuzumab
Brentuximab vedotin
Autologous PBSCT, mini‐allograft
Zanolimumab
IVA, IVB
TSEB or radiotherapy, chemotherapy
HDAC‐inhibitors (vorinostat, romidepsin)
IFN‐α
Bexarotene
Denileukin diftitox
Low‐dose MTX
Alemtuzumab
Brentuximab vedotin
Palliative
Autologous PBSCT, mini‐allograft
Zanolimumab
Cutaneous B‐cell lymphoma
Type
Clinical
Immunophenotype
5‐year survival
Marginal zone
Often solitary lesions on trunk or extremities, possible Borrelia association, tattoo association
BCL2+ BCL6− CD10− IRTA1+
>95%
Primary follicle center
Often solitary/grouped plaques on scalp/forehead or trunk
BCL2− BCL6+ CD10± *
>95%
Diffuse large B‐cell
80% on leg of elderly patients, F>M
BCL2+ BCL6+ CD10– MUM1/IRF4+
50%
Other B‐cell lymphomas – Intravascular large B‐cell lymphoma, Lymphomatoid granulomatosis, CLL (ZAP‐70+), Mantle cell lymphoma, Burkitt lymphoma, and B‐lymphoblastic lymphoma.
Leukemia cutis
Monoclonal Gammopathies in Dermatology
Disease
Ig type
Direct cutaneous infiltration of cells causing monoclonal gammopathy or depostion of cell products
Waldenstrom
IgM
AL amyloidosis
IgG
Multiple myeloma
IgG
Plasmacytoma
IgA
Cryoglobulinemia
IgM
Disorders associated with monoclonal gammopathies
Scleromyxedema
IgG λ
Schnitzler
IgM κ
POEMS
IgA > IgG
Scleredema
IgG κ
Plane xanthoma
IgG
EED
IgA
NXG
IgG κ
Pyoderma gangrenosum
IgA
Sneddon–Wilkinson
IgA
IgA pemphigus
IgA
Sweet
IgG
Tumors and gene associations
Tumor
Gene
Protein
Comment
Anaplastic large cell lymphoma, primary systemic
NPM‐ALK fustion
Nucleophosmin‐anaplastic lymphoma kinase fusion protein
T(2:5)(p23;q35); ALK+ systemic anaplastic large cell lymphomas have better prognosis than ALK− systemic large cell lymphomas (primary cutaneous cases are ALK−)
Basal cell carcinoma
PTCH2
Patched
Somatic and BCNS
Clear cell sarcoma
EWS‐ATF1
Fusion of Ewing sarcoma and activating transcriptions factor 1
aka “malignant melanoma of the soft parts”
Dermatofibrosarcoma protuberans
COL1A
PDGF
Collagen 1A
Platelet‐derived growth factor
t(17;22)(q22;q13), may have supernumerary ring chromosome
Hypereosinophilia syndrome
FIP1L1‐PDGFRA
F/P fusion
~Chronic eosinophilic leukemia
Mantle cell lymphoma
T(11;14)
Fusion of Bcl‐1/Cyclin D1 and immunoglobulin heavy chain
Tumor cells originate from the “mantle zone” of the lymph node; associated with men over the age of 60
Mastocytosis
KIT
C‐kit
Adult but not childhood forms
Melanoma*
CDKN2A/p16‐INK4A/p14‐ARF, BRAF, KIT, NRAS, MITF, PTEN, AKT, MC1R, APAF‐1
BRAF often mutated in melanoma and benign melanocytic nevi but unusual in Spitz nevi (similar to NRAS but reverse w/ HRAS); BRAF and NRAS mutations are reciprocal; BRAF phosphorylates ERKs/MAPKs; MC1R mutations impair cAMP synthesis; p16‐INK4A inhibits Rb; p14‐ARF inhibits p53 degradation
Merkel cell carcinoma
Trisomy 6
Mycosis fungoides
CDKN2A, TNFRSF6 (Fas), JUNB
P16 (INK4a), P14 (ARF)
Largely tumor suppressors
Pilomatricoma
CTNNB1
Β‐Catenin
Activating mutation; wnt signaling pathway
Seborrheic keratosis
FGFR3, PIK3CA
FGF receptor 3, Phosphatidylinositol kinase 3, catalytic, alpha
Same genes as epidermal nevi
Spitz nevi
11p amplifications
HRAS
Minority of Spitz have HRAS mutations, but much more often than in melanoma
SYSTEMIC AND METABOLIC DISEASES
Amyloidoses
Classification
Type
Symptoms/Subtypes
Primary systemic
AL ≫̸AH
40% have skin involvement: waxy skin‐colored papules (nose, eyes, and mouth), alopecia, carpal tunnel, pinch purpura, shoulder pad sign. Also may deposit in heart, GI tract, and tongue.
Secondary/reactive systemic
AA
Skin NOT INVOLVED. Deposits in liver, spleen, adrenals, and kidney. Associated with chronic disease: especially TB, leprosy, Hodgkin, RA, and renal cell cancer.
Primary cutaneous
AL
Nodular amyloid: nodule(s) on extremities, trunk
Keratin
Macular amyloid: pruritic macules interscapular region, associated with nostalgia paresthetica
Keratin
Lichen amyloid: discrete papules on shins
Secondary cutaneous/tumor associated
Keratin
Following PUVA and in neoplasms
Familial syndromes
AA
Hereditary periodic fever syndromes: Familial Mediterranean fever and TNF receptor‐associated periodic syndromes (but not Hyper‐IgD)
AA
Cryopyrin‐associated periodic syndromes: Familial cold autoinflammatory, Muckle–Wells, CINCA/NOMID
Amyloid subtype
Association
AL
Ig light chain
Primary systemic, myeloma, plasmacytoma, nodular
AH
Ig heavy chain
Primary systemic, myeloma
AA
(apo) serum AA (SAA)
Reactive systemic, TRAPS, FMF, Muckle–Wells, familial cold autoinflammatory
ATTR
Transthyretin (prealbumin)
Familial amyloid polyneuropathy 1 and 2, Familial amyloid cardiomyopathy, Senile systemic
A β2M
β2‐microglobulin
Hemodialysis
A β
A β precursor protein (AβPP)
Alzheimer, Down, Hereditary cerebral hemorrhage with amyloidosis (Dutch)
Keratinocyte tonofilaments
Macular and Lichen, MEN IIa, Secondary cutaneous (PUVA, neoplasms)
Apolipoprotein I
Familial amyloid polyneuropathy 3
Atrial natriuretic factor
Isolated atrial
Calcitonin
Medullary thyroid cancer associated
Cystatin
Hereditary cerebral hemorrhage (Icelandic)
Fibrinogen α chain
Familial fibrinogen associated
Gelsolin
Familial amyloid polyneuropathy 4 (Finnish)
Islet amyloid polypeptide
Diabetes mellitus II/Insulinoma associated
Lactoferrin
Corneal lactoferrin associated
Lysozyme
Familial lysozyme associated
Medin/Lactadherin
Aortic medial
Prion Protein/ Scrapie
Creutzfeld‐Jacob
Histiocytosis
Histiocytosis
Onset
Clinical features
Associations
Pathology
Langerhans Cell Histiocytosis 2/3 children age 1–3 yo; 1/3 adults – usually pulmonary, often smokers. New classification by organ of involvement:
Letterer–Siwe
0–2 yo
ALL, solid tumors
Hand‐Schüller‐Christian
2–6 yo
Eosinophilic granuloma
Older children/adults
Hashimoto–Pritzker
Congenital
Non‐Langerhans Cell Histiocytosis w/o Malignant Features
Juvenile xanthogranuloma
Early childhood
Benign cephalic histiocytosis
0–3 yo
Probably same as JXG
aka Histiocytosis w/ intracytoplasmic worm‐like bodies (on EM)
Generalized eruptive histiocytoma
Adults > children
Indeterminate cell histiocytosis
Adults > children
Antigenic markers of both LCH and non‐LCH
Multicentric reticulohistiocytosis
Adults (F > M) 30–50 yo
Giant cell reticulohistiocytoma, aka solitary reticulohistiocytoma = isolated, cutaneous tumor version of MRH
Necrobiotic xanthogranuloma
Sixth decade
Xanthoma disseminatum
Any
Rosai–Dorfman Dorfman
aka Sinus histiocytosis with massive lymphadenopathy
10–30 yo, M > F
Erdheim–Chester
Middle age
Hemophagocytic lymphohistiocytosis
Children
Sea‐blue histiocytosis
Inherited
Large, azure blue, cytoplasmic granules with May‐Gruenwald stain (yellow‐brown on H&E, dark blue with toluidine or Giemsa)
Non‐Langerhans Cell Histiocytosis with Malignant Features
Malignant histiocytosis
M > F 2:1
Variable
Xanthomas
Type
Distribution/appearance
Associations
Xanthelasma palpebrarum
Polygonal papules esp. near medial canthus
May be associated with hyperlipidemia (50%) including any primary hyperlipoproteinemia or secondary hyperlipidemias such as cholestasis
Tuberous xanthomas
Multilobulated tumors, pressure areas, extensors
Hypercholesterolemia (esp. LDL), familial dysbetalipoproteinemia (type 3/broad beta dz), familial hypercholesterolemia (type 2), secondary hyperlipidemias (nephrotic syndrome, hypothyroidism)
Tendinous xanthomas
Subcutaneous nodules esp. extensor tendons of hands, feet, Achilles, and trauma
Severe hypercholesterolemia (esp. LDL), particularly type 2a, apolipoprotein B‐100 defects, secondary hyperlipidemias (esp. cholestasis, cerebrotendinous xanthomatosis, and beta sitosterolemia)
Eruptive xanthomas
Crops of small papules on buttocks, shoulders, extensors, and oral
Hypertriglyceridemia (esp. types 1, 4, and 5 hyperlipidemias), secondary hyperlipidemias (esp. DM2)
Plane xanthomas
Palmar creases
Familial dysbetalipoproteinemia (type 3), secondary hyperlipidemia (esp. cholestasis)
Generalized plane xanthomas
Generalized, esp. head and neck, chest, flexures
Monoclonal gammopathy, hyperlipidemia (esp. hypertriglyceridemia)
Xanthoma disseminatum
Papules, nodules, and mucosa of upper aerodigestive tract
Normolipemic
Verucciform xanthomas
Solitary, oral or genital, adults
Normolipemic
Hyperlipoproteinemias: Fredrickson classification
Type
Name
Defect, AR/AD
Lipid profile
Xanthomas
Other clinical
I
Hyperlipoproteinemia
Lipoprotein lipase, AR
↑ Chylomicrons, chol, TG
↓ LDL, HDL
Eruptive xanthomas (2/3), lipemia retinalis
↑ CAD, HSM, and pancreatitis
IB
Apolipoprotein C‐II deficiency
APOC2 AR
Similar to lipoprotein lipase deficiency
IIA*
Familial hypercholesterolemia, LDL receptor disorder
LDL receptor, AD
↑ LDL, chol, TG
Tuberous, intertriginous, tendinous, planar xanthomas, xanthelasma, and corneal arcus
↑ CAD
Familial hyper‐cholesterolemia, type B
APOB, AD
Same as IIA
IIB
Combined hyperlipoproteinemia
Heterogeneous
↑ LDL, VLDL, chol, TG
Xanthomas rare
↑ CAD
III
Familial dysbetalipoproteinemia, Broad betalipoproteinemia
APOE, AR
↑ Chylomicron remnants/VLDL, chol, TG
Planar palmar crease, tuberous xanthomas, and xanthelasma
↑ CAD, DM2
IV
Carbohydrate‐inducible lipemia
AD
↑ VLDL, TG
↓ HDL
Tuberoeruptive xanthomas
↑ CAD, DM2, obesity, etoh, hypothyroidism, pancreatitis, uremia, myeloma, nephrotic, hypopituitarism, and glycogen storage type I
V
Mixed hyperprebeta‐lipoproteinemia and chylomicronemia
APOA5, AR/AD
↑ Chylomicrons, VLDL, TG, chol
↓ LDL, HDL
Eruptive xanthomas, lipemia retinalis
Abd pain, pancreatitis, DM2, HTN, hyperuricemia, OCPs, etoh, and glycogen storage type I
Vitamin Deficiencies/Hypervitaminoses
Vitamin A
Vitamin B1 – Thiamine
Vitamin B2 – Riboflavin
Vitamin B3 – Niacin/Nicotinic acid
Vitamin B6 – Pyridoxine
Vitamin B12 – Cyanocobalamin
Vitamin C
Vitamin D
Vitamin K
Zinc deficiency
Biotin deficiency
Essential fatty acid deficiency
Copper
Selenium deficiency
Lycopenemia
Carotenemia
Kwashiorkor
Marasmus
PEDIATRIC AND PREGNANCY DERMATOLOGY
Vascular tumors and malformation
Vascular tumor
Vascular malformation
Infantile hemangioma
Congenital hemangioma
Kaposiform hemangioentothelioma; tufted angioma
Arterial/capillary/venous/
lymphatic combined lesions (see below)
Presentation
10–15 d after birth
30% present as red macul
Commonly large at birth
At birth or few days after birth
Present at birth
Growth
Rapid growth till 6 mo then slow growth till 1 yr of age
Superficial, deep, or mixed
No growth
Slow growth during childhood, can be locally aggressive
Growth proportional to child’s growth
Involution
Slow, spontaneous involution
30% by age 3, 50% by age 5, 70% by age 7, 90% by age 9
Rapidly involuting congenital hemangioma (RICH) – usually regress completely by age 2.
Non‐involuting congential hemangioma (NICH)‐ No involution
No involution
No spontaneous regression
Histology
GLUT‐1: positive
GLUT‐1: negative
GLUT‐1: negative; KMS: positive
GLUT‐1: negative
Vascular malformation
Slow flow
Fast flow
Combined
Presentation
Capillary (Port wine stain, salmon patch, nevus flammeus)
Venous
Lymphatic
Arterial
AV malformation (congenital)
AV fistula (acquired)
Capillary‐venous
Lymphatic‐venous
Capillary lymphatic venous
Capillary arterivenous
Capillary lymphaticarteriovenous
Infantile Hemangioma (IH) Management
P
Posterior fossa malformation
Dandy–Walker, cerebellar hypoplasia/dysplasia
H
Hemangioma
Facial or neck hemangioma >5 cm
A
Arteriral anomalies
Dysplasia or hypoplasia of the large cerebral arteries
C
Cardiac defects
Coarctation of the aorta, cardiac defects
E
Eye abnormalities
Optic nerve hypoplasia, posterior segment abnormalities
S
Sternal clefting and supraumbilical raphe
Sternal defect/cleft. Supraumbilical raphe
Propranolol Treatment for Infantile Hemangioma
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